JOURNAL TRANSCRIPT
CNSNewsletter September 2014
Topic
September 2014 – Volume 07, Issue 03
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Editorial
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How Much of Ourselves Are We Born With?
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Lamarck’s Last Laugh: The Nurture Within Your Genome
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Messing up With Mendel
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To Do or Not To Do: Prenatal Testing and Its Ethical Issues
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The Kaspar-Hauser-Syndrome
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Sex Similarities and Gender Differences
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Can You Raise Your Kids Gay?
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The Origins of Intelligence
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White Bears, Written Words: Can Reading Change Our Brains?
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Big, Bigger, Obese
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Sprinters, Swimmers, and Bellybuttons
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Eat Well and Sleep Sound, in These Two Good Health Abound
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Tracing the Roots of Aggression
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Family Shapes Susceptibility to Drug Abuse
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Let Kids Be Kids
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Death in a Bottle
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The Development of Taste Preferences
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Environment and Genetics in Autism
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How to Overcome Your Fate
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Understanding the Pathogenesis of Parkinson’s Disease
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Giving Birth to Epilepsy
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The Perpetrator of Schizophrenia
14 Student Parade Marietta Zille: The Driving Force Behind our Newsletter
CNSNewsletter September 2014
Bye-bye!
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fter 4 years of work and 18 issues of the CNS newsletter, I would like to say good-bye to our beloved readers. But it is only me, Marietta, who will leave, as I am going to do my postdoc in the US – the newsletter will survive! With Apoorva and Ahmed as new editors-in-chief, the newsletter will continue to grow and bloom! And maybe, you can read the occasional article from me. My final wish for the newsletter before I leave was to try make it a little more engaging and zestful. Thanks to Benedikt, we started to work together with Julia Staykova from Scriptorium Consulting, who is an expert on writing and communication skills. In July, our frequent writers and editors gathered to get a brief but intense overview about modern reading habits. Did you know that the average attention span of online readers in 2013 was only 8 seconds?!. We talked about how to improve our articles, a) to make them easier to read for the faster readers that most of us probably are, and b) to make them more visually attractive. We think and hope you can notice the difference — and if you want to learn these skills, join our writing team! This will not only help you to write for the general public, but also for science. But now, let’s turn to our current issue. With several excellent articles from motivated writers, I am proud to tell you of a new record we have reached: With 28 pages, this is our largest issue ever! A big thank you to all our contributors. The topic itself is equally fantastic! Why are we how we are? What determines our behavior, intelligence, sexuality or predisposition to disease? How much is genetic? How much can we influence by altering our environment, food, and behavior? Do I have to say more? Just immerse yourself in these great articles and make up your own mind.
23 Dr. Harebrained Knows it All... Why Is It Again That We Cry When We Are Sad?
23 Check This Out
Enjoy reading! – Marietta, Editor-in-Chief
Research Assessment Without the Journal Impact Factor
24 Conference Report 14th Annual Meeting of the Vision Sciences Society
24 Course Watch Hunting for Cajal’s Butterflies
25 Brain in Press Human Brain Project Controversy Social Conformity May Only Be Short-Term Crayfish Have Feelings Too Europe Suffers from Academic Doping Capsaicin Receptor May Trigger Asthma Attacks
25 A Taste of Home Cat Café
26 Short Story The Gift
28 News in Brief & Whazzup? 28 Imprint
From the left, top row: Bettina Schmerl, Apoorva Rajiv Madipakkam, Claudia Bentz, Ahmed Khalil Lower row: Veronika Lang, Marietta Zille, Betty Jurek, Constance Holman Not in picture: Andreas Antonios Diamantaras, Ann-Christin Ostwaldt, Carla Wood, Filip Morys, Jennifer Flynn, Judith Houtman, Julia Rummel, Laura Empl, Luke Tudge, Rick Cornell Hellman, Yasmine Said
2014 International Graduate Program Medical Neurosciences
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CNSNewsletter September 2014
How Much of Ourselves Are We Born With? Revisiting the Nature Versus Nurture Debate
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he phrase ‘nature versus nurture’ is twins, who share identical genetic inforderived from early studies on the mation, over portions of their lives gives effects of parenting on childhood us insights into the contribution of the development. Researchers sought to de- environment in developing these chartermine the relative contributions of an acteristics. In terms of psychological traits, sepaindividual’s innate qualities, determined by one’s genes (nature), and parenting rated twins usually grow up to be very or personal experiences (nurture) on similar even when brought up in subthe psychological and behavioral traits stantially different environments. In the of children. If a child shows aggressive landmark Minnesota Twin Study, which behavior, was he or she genetically ‘pro- began in 1979, researchers studied more grammed’ to behave in such a way, or is than 100 sets of twins or triplets that it the product of his or her upbringing had been separated in infancy and raised or environment? Consider if one of the apart from one another. They found that child’s parents is also aggressive. Did genetics can explain up to 70 % of the the child acquire this behavioral trait variability in personality, intelligence, through exposure to his or her parent's and temperament between the twins [1]. behavior or through inheritance? No concept is as pervasive in the Implications Beyond Medicine study of health and disease as distin- Investigating the relative contributions guishing the effects of internal and ex- of innate and acquired factors in huternal stimuli on bodily function. Since man psychology and health can have Claude Bernard elegantly introduced far-reaching consequences. Not surpristhe idea, it has not only formed the ba- ingly, the nature versus nurture debate sis of modern physiology but has also has also made its way to the courtrooms. helped us understand numerous patho- Many experts believe that criminality, logical states in terms of the interaction for example, is a trait that is predomibetween inherited and environmental nantly inherited. Thus, defense lawyers sometimes argue (with varying degrees factors. Over the years, the controversy has of success) that, in certain cases, people extended beyond childhood behavior to accused of committing crimes cannot intelligence, sexual preference, and the be held responsible for their actions bepropensity for certain diseases (see “The cause they cannot be held accountable Origin of Intelligence” on p.10 and “Can for their DNA. The discovery of rare mutations that You Raise Your Kids Gay?” on p.15). Despite being heavily researched, at least strongly predispose to aggression, such two problems make the nature versus as that of the monoamine oxidase type nature debate a major challenge facing A gene, has helped encourage the acmodern biology. The diseases and traits ceptance of such legal arguments [2] being investigated, particularly those (see also “Tracing the Roots of Aggresto do with the brain, are themselves sion” on p.16). Biologists and physicians complex and often hard to characterize. often oppose legal battles that attempt Moreover, as our understanding of biol- to make use of such a defense. They ogy progresses, separating the conse- believe that the public often poorly unquences of intrinsic and extrinsic factors derstands the link between genes and on a certain physiological or pathologi- behavior, which is a complex issue. cal state becomes increasingly difficult. Is the Debate Obsolete? Over the past few decades, we have Shedding Light on the Issue Using made some astounding discoveries reTwin Studies Separating the effects of genes and en- garding how our genetic material is vironment on childhood development controlled. We now know that DNA is and the pathogenesis of diseases can not the rigid, unchanging blueprint of be achieved by performing adoption and our entire lives that it was once thought twin studies. Francis Galton first pro- to be. Gene expression is a flexible (yet posed this approach in 1875. It gained tightly regulated) process that is moduimpetus at the beginning of the 20th lated continuously in health and disease. century when Gregor Mendel’s insights Epigenetics (meaning ‘in addition to’ into the mechanism of heredity became genetics) is the field of biology that deals widely known. Identifying differences in with the alterations in gene expression specific traits by studying monozygotic that occur in the absence of changes
Source: Eric Peacock, Flickr, http://bit.ly/1tgOoaU
to the DNA sequence. These changes can persist over long periods of time and, perhaps most interestingly, can be inherited from one generation to the other. The signals that trigger epigenetic changes can come from within the organism itself or from the surroundings (see “Lamarck’s Last Laugh” on p.4). The more we learn about epigenetics, the smaller the distinction between nature and nurture becomes. Consider an example. Exposing an individual to stress can alter the expression of proteins involved in the pathogenesis of mood disorders [3]. This altered expression can persist not only throughout the individual’s lifetime, but can also be transmitted to his or her offspring. If one of this individual’s children eventually develops depression, is the contribution of the exposure of the child’s parent to stress inherited or environmental? The simple answer is both. It thus comes as no surprise that, nowadays, many experts consider the debate obsolete. Although we should not insist on drawing a line where boundaries are becoming less and less clear, making a distinction between the effects of nature and nurture aids our understanding of complex biological processes. [ 1] Bouchard TJ Jr et al, Science, 1990 [2] Brunner, Nelen et al, Am J Hum Genet, 1993 [3] Murgatroyd, Nat Neurosci, 2009
Ahmed Khalil, MSc student, Erasmus Mundus Neurasmus www.medical-neurosciences.de
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CNSNewsletter September 2014
Lamarck’s Last Laugh
The Nurture Within Your Genome
Source: wikimedia commons, http://bit.ly/1s6NBdw
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lthough long abandoned as a pri- and may subsequently be inherited mary approach to explaining evo- for generations [4]. Because epigenlution, Jean-Baptiste Lamarck’s etic modifications are acquired during theory of inheritance may today be the lifetime of an organism and can be revitalized through the phenomena of passed down directly to the offspring, epigenetic inheritance. As early as 1809, they are inherited in a Lamarckian, rathLamark proposed that an individual or- er than a Mendelian fashion. The ways in ganism may pass on traits it acquired which both of these forms of inheritance during its lifetime to its offspring [1]. influence our genome blend both nature From a fundamental Lamarckian per- and nurture, determining who we are. spective, if a short-necked giraffe has trouble reaching leaves high up in the You Are What You Eat... And Fear trees, it will develop a longer neck and Recent studies have shown many fascipass this valuable trait along to its chil- nating instances in which acquired bedren. havioral and physiological traits are inYears later in 1859, Lamarck’s theory herited epigenetically. Along with many was made obsolete by Darwin's theory other supporting studies, Felicia Nowak of natural selection from his famous and colleagues showed in 2013 that book, On The Origin of Species. Natural obese rats pass on epigenetic changes selection, he wrote, is the evolution of to their offspring that increase their populations through the reproductive propensity to obesity [4]. Pesticide exsuccess of organisms with spontaneous- posure has also been shown to alter epily arising advantageous traits that they genetic patterns over generations. After are then able to pass on to their off- treating pregnant mice with the fungispring. [2] This continues to be the ac- cide Vinclozolin, testicular abnormalicepted theory today of how organisms ties were observed for five generations. adapt to the environment and evolve This correlated with abnormal methylaover time. tion patterns in offspring for both genMendel’s experiments in the pea ders [5]. plant in the late 19th century supported In addition, recent findings show that Darwin’s theory, and contradicted La- mice can inherit the fear of a smell that marck’s by illustrating how organisms their parents were classically condiinherit traits through discrete genes tioned to fear. Ten days before mating, passed on from parents to offspring [3]. parent mice were exposed to acetopheFurthermore, the field of molecular ge- none, a chemical found in many fruits netics from the 1950’s has shown how and food additives, while receiving mild these genetics traits can change over foot shocks. Despite never having been generations through random mutation. exposed to the scent, offspring retained innate fearful behavior in its presence The Key to Fast Transmission for three generations. Further, these It was not until the discovery of epi- patterns could be linked to abnormal hygenetics that scientists elucidated how pomethylation of an olfactory receptor the genome might change over the gene [6]. This latter epigenetic example course of a lifetime in response to en- provides a logical mechanism for how vironmental stimuli [4]. Although most an organism passes on important geepigenetic alterations are erased during netic information to their progeny. An the genetic reprogramming of an em- innate fear of a scent forewarned these bryo, not all of these marks are removed, mice about a possible sign of danger. 2014 International Graduate Program Medical Neurosciences
Lamarck and Darwin Toe to Toe Lamarck is not in the clear quite yet. Many questions and criticisms remain about the inheritance of epigenetic changes. In humans, there are many correlations shown between specific epigenetic findings and ancestral exposure to chemicals or famine. Yet, only few causative links have been made thus far. More information is needed to confirm the existence of epigenetic inheritance in humans, to clarify how many generations these changes last, and to determine the power they have to elicit a phenotype. In the debate between Mendelian and Lamarckian inheritance, it is still a mystery why we need both mechanisms, and in which situations each is most important. Lamarckian inheritance via epigenetic transmission may serve the purpose of quick adaptation. It allows for a dynamic genome that may quickly be modified in response to sudden environmental changes. Mendelian inheritance, in contrast, requires random mutations that cause a species to evolve slowly over generations. Perhaps this process is too slow to prevent the extinction of a species without a supporting mechanism of adaptation such as epigenetic changes. The epigenome may provide more genetic variation from which natural selection can choose. The balance of these two systems reflects the complex relationship between populations and their environment. Seeing nature and nurture collide in the field of epigenetics is equally empowering and frightening; we now know one way in which our everyday decisions, actions, and exposures to the world may influence generations to come.
[ 1] UCMP Biography of Lamarck, http://bit.ly/1gBLkQ9 [2] Understanding Evolution, http://bit.ly/1puUt0O [3] Mendel’s Genetics, http://bit.ly/1ifkwnZ [4] Slyvka et al, Endocrine, 2014 [5] Strouder et al, Reproduction, 2010 [6] Dias and Ressler, Nat Neurosci, 2014
Carla Wood, MSc student
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CNSNewsletter September 2014
Messing up With Mendel
Genetic Imprinting and Its Effect on Your Life
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t was on a summer’s day in the year advantages of a diploid 1822 when Johann Mendel saw the genome, it is unclear why light of day. He inherited 50 % of his genetic imprinting occurs. genes from his father Anton and 50 % The most favored hypothfrom his mother Rosina. But contrary esis is the “parental conto his postulated rules, the expression flict theory”. It states that of some genes was altered in a parent- genomic imprinting reof-origin specific manner: Depending flects the differing strateon whether the origin of a gene copy gies of parents regarding is maternal or parental, the gene is ac- the proliferation of their tive or non-active. This phenomenon is genes [4]. called “genetic imprinting” or “genomic A classic example is the imprinting” [1]. regulation of fetal growth in mice by imprinting of Methylation Is Key to Genetic the insulin-like growth Imprinting factor 2 gene (Igf2) and Helen Course described a “parent-of- the receptor gene Igf2r. origin effect” for the first time in 1960. Igf2 is a paternally exExperiments with mice in 1980 revealed pressed growth factor the first proof of parent-dependent in- that enhances fetal and heritance of some genes. They used placental growth when it binds to the
Activation of imprinted genes is origin-dependent nuclear transplantation in mouse embryos with either maternal or parental chromosomes. The embryos could not develop normally, despite a diploid genome [2]. Since this discovery, researchers have tried to answer questions on how imprinting is facilitated, what the evolutionary advantages are, and which diseases are correlated with imprinting. In principle, imprinting is an epigenetic process that leads to monoallelic expression without altering the DNA sequence – a process known as methylation that leads to inactivation of gene expression (see also “Lamarck’s Last Laugh” on the left). In contrast to mutation, imprinting is reversible. During gametogenesis, the imprinting status in germ cells is erased and re-programmed according to the sex of the individual [3]. A Parental Tug-of-War As genetic imprinting diminishes the
receptor Igfr1. Therefore, paternal strategy lies in extracting more resources to improve the fitness of their offspring [2]. The maternally expressed receptor Igf2r also binds Igf2 which leads to degradation of the paternally expressed protein. This antagonistic mechanism counterbalances the paternal effect and ensures an equal distribution of nutrients among the offspring [2]. Loss of genetic imprinting in Igf2- or Igf2r-locus in mice leads to either fetal overgrowth (e.g., biallelic expression of Igf2) or reduced fetal growth. The Shady Side of Genetic Imprinting In humans, less than 1 % of the human genome is modified by parental imprinting [4]. The majority of these genes are related to growth and neuronal development of the embryo [4]. By affecting neurodevelopmental processes, genetic imprinting influences brain function and behavior. This leads to severe dysfunc-
Principles of Mendelian Inheritance Mendel’s studies with pea plants established many rules of heredity, known as rules or principles of Mendelian inheritance: 1. Segregation: In diploid organisms, chromosome pairs are separated into individual gametes to transmit genetic information to offspring. 2. Independent Assortment: Alleles on different chromosomes are distributed randomly to individual gametes. 3. Dominance: A dominant allele completely masks the effects of a recessive allele. A dominant allele produces the same phenotype in heterozygotes and in homozygotes.
Source: Betty Jurek
tions if the non-imprinted gene copy is malfunctional. The ubiquitin-protein ligase E3A (UBE3A), for example, is only imprinted in brain tissue where the paternal copy is silenced. This enzyme is a key player in ubiquitin-mediated protein degradation. Children with a malfunctional maternal copy suffer from Angelman’s syndrome, characterized by developmental delay, epilepsy, movement disorders, and a perpetually smiling facial expression. Other genes located near the UBE3A locus, like the genes SNRPN and NDN, are maternally imprinted. A malfunctional paternal copy leads to Prader-Willi syndrome, characterized by intellectual delay, hypogonadism, and hypotonia [4]. The risk of some neuropsychiatric disorders such as autism spectrum disorders, schizophrenia, Tourette syndrome, and bipolar disorders has also been related to genetic imprinting [4]. It seems that genetic imprinting can influence many aspects of our lives. Further investigation will bring us a better understanding of development, pathologies, and genetic fitness. And though it contradicts with Mendel’s postulated rules, he would probably be fascinated by the strange paths evolution may take. [ 1] http://www.genetics.edu.au [2] Reik and Walter, Nat Rev Genet, 2001 [3] Philips, Lobo, Nature Edu, 2008 [4] Wilkinson et al, Nat Rev Neurosci, 2007
Betty Jurek, PhD student, AG Prüß www.medical-neurosciences.de
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CNSNewsletter September 2014
To Do or Not to Do: Prenatal Testing and Its Ethical Issues
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healthy couple is expecting their from the Greek words eu, first child. The woman is 34 years meaning ‘good’, and -genēs, old and is 16 weeks pregnant. Al- meaning ‘born’. It refers though she carries no major risk fac- to the practice of improvtors, she and her partner decide to opt ing the genetic quality of for prenatal testing. The results of the the human population [2]. tests show that their baby girl has Turn- This philosophy advocates er syndrome. This is a genetic disorder the promotion of higher rewith a missing X chromosome leading production of people with to abnormalities such as short stature, positive traits (positive eudysfunctional gonads, and problems genics) and the reduced rewith the kidney, thyroid, and heart. How- production of people with ever, a number of these problems can less-desirable traits (negabe treated. The question for the couple tive eugenics). now is whether they decide to terminate The results of a prenatal the pregnancy or carry the child to full test provides a couple with term. a lot of information about their unborn child. Naturally, one can What is Prenatal Testing? see how this might lead to supporting Prenatal diagnosis refers to tests per- eugenics. It is certainly wrong to abort formed on the unborn fetus with the aim a child based on sex, and some countries of detecting genetic and chromosomal have even taken legal action to prevent abnormalities, as well as birth defects. this practice [3]. However, getting valuThe most common noninvasive proce- able information about the health of dure is an ultrasound. This procedure their child can make a couple more fican provide a lot of information about nancially and emotionally prepared to gestational age, fetal position, and can receive their child. Some birth defects detect abnormalities with up to 90 % ac- like spina bifida can be treated immecuracy. diately after the child is born. Knowing Invasive techniques include amnio- about such conditions in advance can centesis, chorionic villus sampling, and also prepare medical professionals for fetal blood sampling from the umbilical the birth. cord. Amniocentesis can usually be perAnother problem that can arise with the birth of a child with a disorder can be the quality of relationship between Prenatal DNA can be obtained the parents and the child. For example, parents may directly from the woman’s blood not be willing to let their child indulge in certain formed only after the 14th week of preg- activities leading to a restriction in the nancy and takes at least a few weeks for child’s freedom. In addition, for late-onthe results to be obtained. On the other set genetic disorders, the issue of socihand, chorionic villus can be done very etal discrimination from employers and early on in gestation (9-12 weeks) and insurance companies is to be taken into takes only 24 hours for the results [1]. account. However, with such early testing comes What is often forgotten is that being a higher risk to the fetus. a carrier for disease-linked genes does Recently, genetic tests have also not guarantee getting the disease. Often, been developed, making it possible physical and environmental factors can to analyze fetal DNA directly from the influence genetic expression to a large pregnant woman’s blood. But the com- extent. But do the benefits of prenatal mercialization of this latter group of testing outweigh the consequences of tests has spurred a huge legal battle. bringing a helpless baby who you know might suffer into this world? Genetic Testing: Criticisms and Defenses When Should We Test? The major ethical issue about prenatal Prenatal testing is usually advised for testing is that it increases the number older pregnant women, couples who of abortions, potentially supporting have a family history of genetic disorthe tenets of eugenics. Eugenics stems ders or already have a child with a ge-
2014 International Graduate Program Medical Neurosciences
Source: Merge of pixabay http://bit.ly/1kyrlqH and wikimedia commons http://bit.ly/1uerAYf
netic disorder, and couples concerned about a specific disorder that might occur more frequently in their ethnic group [4]. On the other hand, every couple has the right to opt for prenatal testing as it provides valuable information
Older pregnant women are advised to get tested about their child. While a negative result will certainly ease anxiety, a positive result will drastically change the couples’ lives. In addition, like all scientific tests, they are also not free from false positives and false negatives. In general, it is always recommended to speak to a genetic counselor before opting for a prenatal test. The question about whether to test remains a personal matter of conscience, and ultimately, any decision that this couple takes will change their lives forever. [ 1] Alfirevic Z et al, The Cochrane Coll, 2009 [2] National Library of Medicine, 2010 [3] Reproductive Health Matters, 2005, http://www.jstor.org/stable/3776292 [4] http://ubeclu.unibe.ch/insel/ GENETEST.HTML
Apoorva Rajiv Madipakkam, PhD student, AG Sterzer
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CNSNewsletter September 2014
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The Kaspar-Hauser-Syndrome
What Child Neglect Tells Us About Nature and Nurture
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uremberg, Germany, 1828: A sav- to be extremely neglected. Studies age and mysterious adolescent with them show that early life nurturboy named Kaspar Hauser ap- ing is critical for neurodevelopment. If pears in the city. He has little knowl- nurturing is absent for the first three edge of language, and both his gait and years of life before adoption into a sobehavior are reminiscent of a young cial environment, newly made positive child [1]. Very likely, he was imprisoned experiences may not be sufficient to throughout his childhood, and raised overcome the malorganization of the under conditions of extreme depriva- neural system. tion. Kaspar Hauser becomes a famous attraction of the 19th century, scientists Principles of Neurodevelopment and philosophers worldwide study his To understand how deprivation impairs behavior attempting to uncover his ori- behavioral and cognitive capacities, we gin. Some think that he is the prince of need to first understand the principles Baden, who was abducted from his cra- of neurodevelopment: At birth most dle; others claim he is an imposter. neurons are already present, yet they Whatever the truth of Hauser’s life, have to organize into functional syshis case is the oldest documented and tems. Thereby activation of recurrent most famous case of severe childhood patterns appears to be an important deprivation. Extreme hospitalism, or ne- factor. Neurons that are not sufficiently glect-mediated failure of development, activated undergo apoptosis in a ‘use is thus also called “Kaspar-Hauser Syn- it or lose it’ manner. The sculpting and drome”. This malady is characterized by refinement of neural connections is reretarded physical development, percep- solved by dendrite and axon sprouting, tual-motor skills and language as well as followed by synaptogenesis. The latter extreme anxiety. It is caused by sensory process is tightly regulated by growth deprivation and lack of social contact or factors and adhesion molecules, whose abuse during early childhood. expression is regulated by environmenAnother genre of child neglect is the tal cues mediated by the senses. wolf child or feral child, who has lived The brain develops in a sequential isolated from human contact and has fashion; different areas form, organize, no experience of human behavior and and become fully functional at differlanguage. The most famous example ent times during childhood. There are is Mowgly from the fictional story The thus different sensitive periods for Jungle Book. The difference between each brain area and neuronal function. Kaspar-Hauser Syndrome children Disruption of critical cues can alter the and feral children can be seen in their developmental processes and lead to dibehaviour. Feral children behave like minished capabilities in the neural systhe animals with which they lived (e.g. tem for a given sensory modality. Diswolfes), because they have learned their ruption of critical neurodevelopmental behaviour instead of human behaviour. cues can result from (1) lack of sensory Severely deprived Children do not learn experience during sensitive periods any behaviour and are thus even more (e.g., neglect) or (2) abnormal patterns retarded in their perceptual-motor skills of necessary cues due to extremes of and development. experience (e.g., abuse). Studies of Child Neglect As it would be brutal to deprive children of care for the sake of science, most studies rely on case reports of severely neglected children [2]. Thereby, often, the child's medical and social history is unknown. As in the case of Kaspar Hauser, scientists usually do not know the exact form of neglect, or whether neurological defects are a direct consequence. Many studies on hospitalism are based on children raised in badlyrun orphanages [3]. Children who were adopted from Romanian orphanages in the early 1990s were often considered
Clinical Impacts of Child Neglect Disturbed neurodevelopment results in defects in language, motor delays, impulsivity, disorganized attachment, dysphoria, attention deficits, and hyperactivity. Furthermore neglected children have a reduced frontal-occipital circumference, which is an estimate of brain size in young children. Furthermore, CT scans from neglected children show enlarged ventricles or cortical atrophy [4]. MRI studies with maltreated children also demonstrate decreased metabolic activity in a number of brain areas [5].
Abnormal brain development following sensory neglect in early childhood. The CT-scan of a child suffering from severe sensory-deprivation neglect is smaller and shows enlarged ventricles and cortical atrophy.
The severity of neurological issues increases with the time children spend in an adverse environment: The earlier and more pervasive the neglect, the more indelible the deficits. After the children are removed from the neglectful environment, the degree of recovery is inversely proportional to age in which the child was removed from the neglecting caregivers [4]. We learn from these studies that neurodevelopment depends on both nature and nurture. Many functions of the brain result from a complex interplay between genetic potential and appropriately timed experiences. Child neglect – defined as the absence of input in critical periods of development – leads to abnormalities in cognitive, emotional, behavioral, and social functioning. Healthy neurodevelopment depends upon attentive nurturing during infancy. To make sure stories like Kaspar Hauser’s and similar horrible stories of child neglect don’t happen again, social services provide help for families where neglect is suspected. If parents are unable to meet their children’s needs then professionals intervene to safeguard the child’s welfare. As stimulation of a child’s senses in the early infancy is so important, it is neccessary to act early if child neglect or abuse is suspected. No issue cries out for a more immediate and allencompassing response than ensuring the safety and well-being of our children – our hope for the future. [ 1] Feuerbach, 1835 (Klett, 1963) [2] Spitz, Psychoanal Study Child, 1945 [3] Barth Spiegel, 1990 [4] Perry, Brain and Mind, 2002 [5] Chughani et al, Neuroimage, 2001
Claudia Bentz, PhD student, AG Eickholt www.medical-neurosciences.de
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CNSNewsletter September 2014
Sex Similarities and Gender Differences
Are Women and Men Different or Do They Learn to Be Different? embryonic tissue and work in similar ways. We all secrete the same hormones although there are some variations in hormone levels and patterns. There are no consistent morphological brain differences between the sexes, apart from the slight size and structure differences. The observed variations are much higher across individuals, but not between sexes. Women and men are actually the same species, says Dr. Agustín Fuentes [5]. Do We Explore the World Differently? Predetermined sex variations do exist. But how are those subtle variations related to our behaviors? The other main influence on our behavior are gender stereotypes, which are shaped by a learning process. As we grow up, we
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uman beings have been convinced for centuries that women and men are different from each other. One main argument is that sex differences are largely determined by biological, natural causes – genes, hormones, and brains.
Are We Different Species from the Same Planet? Two chromosomes make us either female (two X) or male (one X and one Y) [1]. Our sex hormones masculinize or feminize some organs as they develop. Most strikingly, we develop very different reproductive systems, which are responsible for the creation of new life. Starting in the womb, our brains acquire subtle differences: 1) overall size – the brain being, on average, 10 % larger in men; 2) overall composition – men have a slightly higher proportion of white matter whereas most of the cerebral cortex has a higher proportion of grey matter in women; 3) structures – the third interstitial nucleus within the hypothalamus is, on average, about twice as large in men [2,3,4].
Women and men are more similar than they are different The core sex differences in our biology are clear, but most of our biological characteristics are more similar than they are different. We share 22 pairs of chromosomes. Our reproductive organs emerge from the same mass of
Cultural Roots of Our Identity Some believe gender differences are created mostly due to cultural influences [4]. In the men-centered gender culture, the view that men are superior to women has often been promoted and acknowledged by the whole society, even by the women themselves. For instance, based on Confucian culture, women should follow the three duties and four virtues (“sāncóngsìdé”), namely: obey the “three men” (father before marriage, husband during married life and son in widowhood), and “four virtues” (morality, physical charm, propriety in speech, and efficiency in needle work). Although gender relationships are changing, such cultural norms are still deeply rooted and firmly implanted in people’s minds.
Gender differences are shaped by a learning process learn society’s norms about how women and men look and act. Many studies have found gender differences in cognitive abilities. Women tend to be more empathetic and perform better on working memory and language tasks whereas men tend to be more aggressive and have superior performance on mental rotation tasks [6]. Findings like these are often exaggerated towards popular notions of women liking chatting and needing special parking spaces. In the BBC News, Tomchak reported that six women drivers take up twelve parking spaces [7]. Many of these claims are accompanied by the assertion that observed brain differences are responsible for supposed gender-based cognitive differences. However, given the complexity of our brain function, it is “fantastically ambitious” to relate any subtle brain-based differences to psychological function, argues Dr. Cordelia Fine in her book Delusions of Gender [8]. Moreover, brain structure and function change in response to experience, so any observed brain differences in sex could also be due to differences in upbringing and socialization. In 2005, Hyde found that 78 % of gender differences are small or close to zero by compiling meta-analyses of psychological tests on about 7 million people. She proposed the gender similarities hypothesis. It suggests that women and men are alike on most – but not all – psychological variables [9].
2014 International Graduate Program Medical Neurosciences
The Zeitgeist of Harmonious Society We are born with a concrete sex, our biological state, but acquire gender, the role we play in society. There is great individual diversity within sexes and societies. Research might tell us more about how sex and gender play out in the dynamic change and whether and how society’s teaching of gender affects neurological processes. As human beings, both women and men make progress not only physically, but also spiritually, not only in the realm of intellect, but also in the realm of wisdom. Research into the similarities and differences between women and men can be used to help reach a new, more profound understanding of sex and gender. It can help us make use of both similarities and differences for the good of all mankind. [ 1] Mank, Trends in Genet, 2013 [2] Ruigrok et al, Neurosci Biobehav Rev, 2014 [3] Whittle et al, Biol Psychol, 2011 [4] Costandi, 50 Ideas You Really Need to Know the Human Brain, 2013 [5] http://bit.ly/1pwiq7O [6] Halpern, Sex Differences in Cognitive Abilities: 4th Edition, 2012 [7] http://bbc.in/1ofw6o0 [8] Fine, Delusions of Gender, 2010 [9] Hyde, Am Psychol, 2005
Shuyan Liu, PhD student, AG Heinz
CNSNewsletter September 2014
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Can You Raise Your Kids Gay?
Uncovering the Roots of Male Homosexuality
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n July 16th 1993, the Daily Mail ran homosexual males have a higher numthe headline: “Abortion hopes af- ber of older brothers. To put it differentter the ‘gay genes’ findings”. The ly, having a son increases the probability author, Jason Lewis, claimed that, thanks of the next male child being homosexual. to recent advances, it might soon be posThis is explained by the maternal imsible to predict the sexual orientation of munity hypothesis. It states that male Source: digitalart / FreeDigitalPhotos.net a baby and give parents the option of offspring immunize the mother to male abortion. Irrespective of the intentions cells, thus producing anti-male antibodof the author and possible implications ies during the next pregnancy with a male. male dormitories. They are told to fellate of this article, let us first consider wheth- The theory posits that those antibodies older boys and swallow their semen (in er this will ever be possible. Since male cross the placenta and blood-brain bar- a belief that it is crucial for their proper homosexuality is much more common rier, changing the brain’s development. development). At a particular age, they in nature than female homosexuality, This, in turn, may cause diverted sexual leave the dormitories and lead a hetmost of the research on sexual orienta- attraction and sexual orientation in the erosexual life that leads to marriage. He tion concerns only male homosexuality. male offspring [5]. This phenomenon is claims that this proves his argument of Years into research on the topic, scien- the most thoroughly established factor homosexuality being just a phase. Yet, tists cannot give a conclusive answer to in the field of human homosexuality [1]. the author fails to mention that activithe question of reasons for our sexual However, we cannot forget that more ties performed in all-male dormitories orientation. Simply put, it does not exist. than half of homosexual males have no might be merely a cultural concept and older brothers [1]. that in no way are they a proof of homoThe Evolutionary Mystery sexuality. Homosexual behavior is natural in the The Neuroscience of Homosexuality Additionally, nurture theorists claim animal world, with over 1500 species Concerning the ‘homosexual brain’, a to have identified characteristic familial practising it [1]. Does this give us a first number of brain regions have been patterns that are supposedly related to clue that biological factors play a crucial shown to be, either functionally or ana- children’s homosexuality. Those include role in establishing sexual orientation? tomically, different in homosexuals com- low paternal presence or high maternal Possibly. In 1991, a twin study conducted pared to heterosexuals. Research has cues in the case of male homosexuality. by Michael Bailey and Richard Pillard showed that among monozygotic male Over 1500 species practice homosexual behaviors twins, one gay brother increased the probability of the second being gay by shown that brain regions such as the in- However, this can be easily reversed – up to 52 % [2]. In contrast, this percent- terstitial nuclei of the anterior hypothal- perhaps those familial patterns were age was as low as 22 % for dizygotic amus show similar anatomy in homosex- caused by the homosexuality of children twins and 11 % for adoptive brothers. ual men as in heterosexual women, that [1]. Hamer and colleagues proposed that an is clearly different from heterosexual Clearly, homosexuality is a multifacXq28 allele influences sexual orientation, men [6]. Yet it must be noted that even eted and extremely complicated pheas its sharing between gay brothers was if homosexual males’ brains are similar nomenon. But why do we even think 64 %, not 50 % as would be expected by to those of heterosexual women, it is not about it? The Daily Mail headline from chance [3]. clear whether those changes precede 1993 seems unnecessarily harsh and, at Yet, evolution would intuitively not the development of homosexuality, or least now, incorrect. We are investigatpromote a gene that is anti-reproductive. whether attraction to males has elicited ing the basis of homosexuality, but can Why would it then survive in our popula- changes in the brain. it have detrimental outcomes? Being tion at all? The hypothesis here is simple able to predict one’s sexual preferences and elegant – the gene that in males Environment and Sexual Orientation might mean denying the right to live. So promotes homosexuality, in females con- In his paper, John Bancroft argues that maybe, we should just let it go and try to tributes to their fecundity. Families with homosexuality is caused by environ- accept that people are different no mathomosexual members have been shown mental factors [1]. He starts with an ar- ter where this difference comes from. to reproduce more than those without gument that homosexual males usually [1]. We must, however, note that genetic experience sexual attraction earlier than [ 1] Jannini et al, J Sex Med, 2010 studies conducted on a large group of heterosexuals. They might therefore de- [2] Bailey and Pillard, Arch Gen participants showed that the genetic velop same-sex attraction because at Psychiatry, 1991 changes can explain only a small fraction this point of time, boys spend most of [3] Hamer et al, Science, 1993 of the occurrence of homosexuality [4]. their time with other boys. This is, how- [4] Mustanski et al, Hum Genet, 2005 [5] Blanchard and Bogaert, Am J ever, only a speculation. If Not Genes, Then What? He goes further and says that homo- Psychiatry, 1996 If genes do not explain 100 % of homo- sexuality is often just a phase in human [6] LeVay, Science, 1991 sexuality, there must be some additional development and that the final phase is factors. Interestingly, a fraction of male heterosexuality. To support his hypoth- Filip Morys, homosexuality might be explained by esis, Bancroft gives an example of a peo- PhD student, Max Planck immunology. A phenomenon called the ple in Papua New Guinea: Young boys Institute for Human Cognitive fraternal birth order effect shows that around the age of ten are taken to all- and Brain Sciences, Leipzig www.medical-neurosciences.de
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CNSNewsletter September 2014
The Origins of Intelligence
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he intelligence quotient (IQ) is the Race over Education or Education best predictor of success in aca- over Race? demia and at work. It also serves as The philosophy of race superiority suga reliable indicator of longevity [1], mak- gests that some ‘types’ of humans are ing the origin of intelligence and the pos- superior from birth because of their linsibility of enhancing it a most interesting eage. Fortunately, this has largely been research topic. unpopular since the abolishment of slavThe theory of multiple intelligences ery in America (1865) and the defeat of proposed by Howard Wagner in 1983 out- Nazi Germany (1945). Following each of lines nine types [2]. Some of them, such these events, the Caucasian and Afroas bodily-kinesthetic intelligence (“body American races began to mingle. With smart”) would be hard to assess using the establishment of racially integrated a written test. Yet, it has been shown schools, it became apparent that Afrothat people who performed well on any Americans showed a lower cognitive single test section, such as linguistic in- ability compared to their white peers [5]. telligence, also score high on other areas [2].
The Recipe for Raising a Genius Is Continuous Practice In 1993, K. Anders Ericsson presented evidence showing that violinists who practiced more than 10,000 hours before their 20th birthday were likely to become professionals [6,8]. This was applied to the mastery of other skills and eventually became known as the 10,000 hours rule. Talent plays a lesser role. A standard IQ test provides no or unreliable results for half of the intelligence types known so far. Intrapersonal intelligence, for example, contributes to good teamwork, stress management, and leadership. However, there is no comprehensive and standardised measure for it [9]. It requires four hours of practice (with coaching and reinforcement), for six days a week, for fifty weeks a year, over ten years will help you master anything! It’s no wonder, really. But honestly, how many of us would volunteer to undergo such rigSource: http://notes.fundersandfounders.com /post/79851864388/9-types-of-intelligence orous training?
Big Brains Mean More Intellect Intelligence positively correlates with the size of the whole brain [1]. However, brain size is limited by skull size and the skull has to pass the birth canal. Complications are hence more likely during the birth of naturally intelligent babies, possibly lowering their survival chances. Moreover, the individual volumes of brain areas are highly heritable [1,3], supporting the theory that nature is more influential on intelligence than nurture. Thus, not surprisingly, in diseases that cause dementia, brain cells are lost and the brain effectively shrinks. Genes for Smartness and Intellectual Disability Intelligence is a polygenetic trait. This year, the University of Edinburgh announced the discovery of the first intelligence gene. A highly active NPTN gene allows adolescents to score higher on intelligence tests [4]. The gene codes for a neuronal synapse protein that plays a role in brain development and neuronal signaling. Surprisingly, the NPTN gene explains only about 0.5 % of the variability in intelligence. Conversely, candidate gene studies have revealed over 282 genes associated with intellectual deficits (formerly known as mental retardation). Results pooled from a number of studies conducted during the last century on human intelligence research indicate that genetic factors are responsible for up to 50 % of differences in intelligence between individuals [1,5].
points at age 5 [7]. This result persisted even after the scientists accounted for the level of parental education and several other factors that might influence child IQ. Similar studies have shown that pollution is a cause of birth defects, childhood behavioral disorders, and rare cancers [7].
This result was partly attributed to their lower socioeconomic status [5], but may have fueled racism in Europe. A post-World War II study in Germany looked at the “occupation babies” of Afro-American and Caucasian American soldiers with German mothers. The IQ of the mixed-race children was 96.5 compared to 97 in Caucasian children [6]. This suggested that inheritance of culture, education, and equal opportunity (rather than race) influence IQ. Dirty Minds at Age 5 Associated with Lower IQ A study published this year showed that the exposure of pregnant women to air pollution released by the burning of fossil fuels can cause birth defects and lower the IQ of their offspring by about 3.8
2014 International Graduate Program Medical Neurosciences
[ 1] Gardner, The Nine Types of Intelligence, http://bit.ly/19kchVz [2] Deary et al, Eur J Hum Genet, 2006 [3] Science Daily, 2007, http://bit.ly/1s8kvcf [4] Desrivières et al, Mol Psychiatry, 2014 [5] Dickens, Future Child, 2005 [6] Blech, Spiegel Online, 2010, bit.ly/1pVTiEV [7] Perera et al, J Public Health Policy, 2014 [8] Ericsson et al, Psychol Rev, 1993 [9] Arora et al, Med Educ, 2010
Rick Cornell Hellmann, PhD student, AG Schwab
CNSNewsletter September 2014
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White Bears, Written Words Can Reading Harness Brain Plasticity?
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nce upon a time in Uzbekistan” Reading Signals from Neuroimaging is not a way that many neurosci- The hills of Uzbekistan are distant from ence stories begin. But for this the labs of today, and indeed, so are issue on nature and nurture, a key nar- the approaches that are used. Although rative began there that would come to many groups worldwide still do not use influence debates up to the present day. written language, they generally aren’t Alexander Luria, a Soviet neuropsy- accessible with an MRI scanner in tow. chologist keenly interested in the rela- So what do we do now? tionship between culture and the mind, Today, our primary knowledge about studied the influence of literacy on styles the effects of reading on the brain comes of argumentation. He wanted to test from longitudinal studies in school-age whether cultural experiences could af- children. These studies [cf 4,5] demonfect thought patterns. By working with strate that literacy appears to co-opt illiterate peasants, he uncovered fasci- pre-existing language networks in the nating examples of how written language brain. Notably, the left superior temposeemed to be necessary for abstract ral sulcus and inferior frontal areas show thought patterns. His most famous ex- robust activation, correlating well with ample went something like this: development of reading abilities. These findings are intriguing, but not entirely Luria: “In the North, there is snow, and conclusive. In the countries where these all bears are white. Novaya Zemlya is studies were performed, children are in the far North. What color are the legally obligated to go to school and rebears there?” ceive formalized instruction. Therefore, Peasant: “I don’t know. I’ve never been a non-literate control group cannot be to the far North. I saw a black bear used to provide more definitive answers here once.” about the effects of literacy on the brain. Recently, researchers have found a Many more such examples (dealing with everything from describing shapes to way around these challenges, to examobjects to self-reference) were collected ine the development of reading skills in in Luria’s bestseller, Cognitive Develop- a more controlled setting. For example, ment: its Social and Cultural Foundations a group in France has published a set of [1]. It went on to be a fundamental text in studies examining the neural correlates of the development of literacy in adults. both neuroscience and anthropology. Essentially, the scientists scanned the brains of adults who had learned to read Putting Text in Context Although literacy has developed too re- in childhood using diffusion tensor imagcently to alter the human genome, it is ing. They compared them with the brains an integral part of most human societies. of adults who had only recently acquired For example, if you are on your computer literacy skills. Vast tissue tracts were aftoday, you will probably scan more than fected, with literacy acquisition leading 500,000 words (not to mention what to elaboration of tempero-parietal conyou see in your time offline) [2]! Further- nectivity [6]. A separate study which compared two more, the practice of reading makes a fascinating case study for the effect of a groups of illiterate adults, one of which very special type of nurture on the brain. received a reading intervention proReading text is a multimodal exercise, gram, found evidence of reading-mediincorporating visual, auditory, and cog- ated changes in early visual processing nitive/predictive elements of language [7]. Other evidence of literacy’s effects comprehension. Luria argued (and many on the brain come from people who today agree) that reading was necessary have reading disorders such as dyslexia. to provide a scaffold for certain types of These individuals, contrary to their norabstract thought [1,3]. While fascinating mally-reading peers, have been shown to on a purely ethnographic basis, studies demonstrate hypoactivation of several such as these still leave many questions superior temporal areas typically associto ponder. Though literacy underlies ated with word processing and semantic many human interactions, it has only de- retrieval [8,9]. Taken together, this work veloped on a widespread basis in the last suggests a tightly interlinked series of few hundred years. Could this relatively regions in the brain that are altered new type of cognitive processing be suf- through learning to read and whose malfunction may underlie a failure to do so. ficient to make changes in our brain?
Source: Mark Larson, Flickr, “Use your library often!”
Literacy: A Thoroughly Complicated Business So can we still stand by Luria 80 years later? Yes and no. Although it appears that literacy skills do foster changes in activation and connectivity, we are still a long way from understanding how these changes might underlie certain types of abstract thought (and beliefs about polar bears). Moreover, there are several obstacles to getting the full picture about reading and the brain. At the end of the day, reading is a fundamentally culture-bound phenomenon. It is deeply influenced by the values and educational emphases of the society in which it develops. As neuroimaging studies progress, we should not forget where all these questions started. Though a trip through the wilderness is certainly not for the faint of heart, it may still be the best way to integrate neuroscientific, ethnographic, and linguistic inquiry. And with a business as complicated as understanding literacy, it may be where we need to return. [ 1] Luria, Cognitive Development: Its Cultural and Social Foundations, 1976 [2] Bunz, “Is the link economy of UK news sites managing or making abundance?” in PDA: The digital content blog, Nov 2, 2009 [3] Nell, Neuropsych Rev, 1999 [4] Berl et al, Brain Lang, 2010 [5] Horowitz-Kraus et al, Front Hum Neurosci, 2014 [6] de Schotten et al, Cereb Cort, 2014 [7] Boltzmann and Rüsseler, BMC Neuroscience, 2014 [8] Christodoulou et al, PloS One, 2014 [9] Eicher and Gruen, Mol Genet Metab, 2013
Constance Holman, MSc student www.medical-neurosciences.de
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CNSNewsletter September 2014
Big, Bigger, Obese
How We Can and Cannot Influence Our Body Weight
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ore and more people in our so- of variation in ciety are labeled obese. No lon- body size is due ger just a problem in Western to genetic facsociety, obesity is rising in developing tors [6]. Howcountries as well. In 2008, half a billion ever, this does adults worldwide suffered from obesity not explain the according to the definition of the World currently exHealth Organization (WHO). In 2012, the panding obesity WHO stated that more than 40 million epidemic. kids worldwide are overweight or obese. Childhood obesity is also associated with ... But This Is a higher risk of obesity in adulthood [1]. Changes in nuBut what is the reason behind the obe- trition and acSource: Nancy White, Flickr, http://bit.ly/1rWsCKn sity epidemic? Can we blame everything tivity patterns on fast food chains and lack of exercise? of children and families over the past A Little Bit of Both Or are there some intrinsic factors in- decades have most likely had the big- Epigenetics also play a role. Some gevolved as well? gest impact on the current childhood netic factors might only come into play obesity epidemic. Family factors are when the right environmental stimuli It’s Not Our Fault ... crucial in the prevention of obesity. are present. Lack of food during pregThe existence of a common ‘fat gene’ Parents that put unreasonable restric- nancy increases the risk of adulthood causing the obesity epidemic is a myth. tions on their children’s diet, pressure obesity, as was shown in Dutch children However, many genes increase the risk their children to eat certain foods, and born in the 1944-1945 famine [9]. Late of being obese. By 2006, only 176 cases excessively monitor the child’s behav- introduction of solid foods reduces the were reported where obesity is directly ior may do more harm than good. Such odds of obesity at the age of 10 years caused by a single-gene mutation. The behavior is consistently linked to pedi- [10]. Adiposity rebound is the point at which body fat levels are lowest and from then on will only increase (usually Overweight parents increase child obesity risk 13x at 5-6 years of age). Having two overweight parents at this time increases the Human Obesity Gene Map shows a to- atric weight gain. On the other hand, risk of obesity thirteen times [11]! tal of 127 obesity candidate genes [2]. leading by example, such as parental Though certain inherited predisposiIdentified genetic abnormalities include intake of fruit and vegetables, encour- tions do exist, our environment is the leptin deficiency, proopiomelanocortin ages healthy nutrition in children. biggest factor when it comes to obesity mutations, and melanocortin 3 receptor Portion sizes and the caloric value risk. Recently, increased luxury, comfort, abnormalities. These mutations all come of foods have increased over the past and meals with higher calories may have with multiple detrimental effects [3]. few decades. Nearly 20 % of the dif- created this epidemic, but it is up to us Control of food intake is intrinsically ference in energy intake is due to in- to change this! organized by our endocrine system. The creased portion size [7]. The increased pancreatic enzyme amylin suppresses added sugar content of foods and bevappetite via brainstem mechanisms. Cho- erages coincides with the obesity epi- [ 1] WHO on overweight and obesity, lecystokinin (CCK) is produced in the in- demic. Several epidemiological studies http://bit.ly/18pCdAN testine and slows down gastric emptying. focusing on this issue conclude that [2] Rankinen et al, Obesity, 2006 This helps you get the satisfying feeling of intake of sugar-sweetened beverages [3] Skelton et al, Pediatr Clin North Am, being full after eating. On the other hand, is strongly correlated with body mass 2011 [4] De Kloet and Woods, Curr Opin the stomach hormone ghrelin stimulates index (BMI). appetite when the stomach is empty. Reduced activity is also a major fac- Endocrinol Diabetes Obs, 2010 Other hormones play an important tor in the obesity epidemic. Sitting on a [5] Crocker and Yankovski, Endocrinol role in long-term control of body weight. couch and watching television increas- Metab Clin North Am, 2009 The pancreatic hormone insulin reduces es the risk of obesity [3]. Lack of sleep [6] Farooqi and O’Rahilly, Arch Dis Child, energy intake. Leptin has the same effect, leads to increased food intake and may 2000 but is produced by adipose tissue. Neuro- reduce physical activity as well (see [7] McConhay et al, J Am Diet Assoc, peptide Y and orexin are produced in the also “Eat Well and Sleep Sound” on 2004 hypothalamus and stimulate appetite. All the right). Meta-analyses calculated an [8] Bayer et al, Sleep, 2009 of these hormones are suggested as neu- increased risk for obesity of 56-89 % [9] Willyard, Nature, 2014 roendocrine targets for obesity therapy for children who sleep less. This is a [10] Seach et al, Int J Obes, 2010 on the molecular level [4,5]. vicious circle, because increased BMI [11] Whitaker et al, Pediatrics, 1998 Classic twin studies in the 1980s and in children is associated with reduced 1990s, which relied on pairs of identical sleep duration due to an increase in Judith Houtman, and fraternal twins, suggest that 40-70 % adipose tissue deposits [8]. PhD student, AG Heppner 2014 International Graduate Program Medical Neurosciences
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CNSNewsletter September 2014
Sprinters, Swimmers, and Bellybuttons
Centre of Mass is Key to Success in Speed Sports
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ow many gold medals would Michael Phelps have won if he had decided to be a runner instead of a swimmer? If Usain Bolt took a dip in the pool rather than a lap around the running track, would he still be a recordbreaking sportsman? According to science, they probably would not be as successful had they chosen a different sport. Professional athletes train in their respective sports for the better parts of their lives. They maintain exercise and dieting plans for years that would break many of us down in days. As a result, they develop a physical prowess that allows them to achieve incredible feats. For many people, however, choosing the wrong sport may mean that they never live up to their true athletic potential. Genetics, which are at least partly responsible for body mass and height, play a crucial role in determining which sports athletes excel at. In fact, the reason why people of certain ethnicities do better at some sports than others may be explained by simple physics [1]. When running, locomotion is achieved as the centre of mass of the body falls forwards from a height corresponding to the distance from the centre of mass (approximately at the bellybutton in humans) to the ground. While swimming, forward locomotion is dependent
on the distance from the bellybutton to the top of the head producing a lever-like mechanism oscillating about the centre of mass and generating water waves. The location of a person’s centre of gravity affects their aptitude for speed sports. Due to their long torsos, white ath-
Athletes, take a look at your bellybutton! letes tend to have lower centres of mass and are often successful at swimming. Black athletes on the other hand usually have high centres of mass (with long, slim limbs) and fare better at running [2]. For all you budding athletes deciding which sport to pursue, it’s always worth taking a look at your bellybutton. [ 1] Charles and Bejan, J Exp Biol, 2009 [2] Bejan et al, Int Journal of Design and Nature, 2010
Ahmed Khalil, MSc student, Erasmus Mundus Neurasmus
Eat Well and Sleep Sound, in These Two Good Health Abound Can Food Intake Influence Our Sleeping Pattern?
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here are few facts in life that are rock solid: food and sleep are among them. Everyone has to sleep – and obviously everyone has to eat. However, do these two fundamental pillars of bodily existence influence each other and if yes, in what way? The WHY and WHEN of sleep is well studied and is known as the two-process-model of sleep-wake regulation. Process S is defined as a homogenic sleep drive which is generated by sleep inducing substances in the brain (WHY). Process C is the circadian clock, which serves as an internal time keeping device. It controls the timing of most of the processes in our body and by regulating “alertness”, it can influence WHEN we get tired.
Timing of food intake influences sleep The master clock in our brain (suprachiasmatic nucleus – SCN) can convey time cues (e.g., light-dark cycle) to the peripheral clocks which are ticking in almost every cell of our body. These in turn are thought to regulate local tissue physiology [1]. Now, this is where it gets interesting, since various metabolites can feed back onto the peripheral clocks and onto the SCN [2].
For instance, if food resources are restricted to a certain time of day, animals can go from being nocturnal to diurnal or vice versa on a behavioral level. This is also mirrored on the molecular level in tissues such as the liver [3, 4]. Knowing how a system works means we can also trick it. For example, after a trans-continental flight, almost everyone suffers from jet lag. One way to adapt quicker is to eat meals corresponding to the local time, therefore already resetting our organ clocks to local time. Conversely, if sleep rhythms and therefore eating rhythms are chronically disrupted, such as in shift workers, this can lead to obesity and other metabolic diseases [5]. All in all, in the hectic pace of modern life, we often neglect our body clocks concerning sleeping and food intake, thereby seriously endangering our health. As the medical psychologist Till Roenneberg said: “Time really is of the essence”. [ 1] Dibner et al, Annu Rev Physiol, 2010 [2] Morris et al, Mol Cell Endocrinol, 2012 [3] Damiola, Genes Dev, 2000 [4] Mistlberger, Eur J Neurosci, 2009 [5] Bass andTakahashi, Science, 2010
Veronika Lang, PhD student, AG Kramer www.medical-neurosciences.de
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Student Parade
CNSNewsletter September 2014
Marietta Zille
The Driving Force Behind our Newsletter
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ho is Marietta Zille? Researcher? Karate champion? President of a voluntary organisation......? Well, the editor-in-chief for over 4 years of the CNS Newsletter, Marietta is not your usual PhD student – she is the prototype of an allrounder! Before she joined the Medical Neurosciences Program for her Masters in 2008, Marietta studied Biology at the University of Cologne. After graduating from the Master program, she went on to continue her PhD in the program. After successfully finishing her PhD this year, she is leaving Berlin to pursue her scientific career at the prestigious Cornell University in the United States. Apart from her primary passion of research, she is involved in several other activities. We’ll use this month’s Student Parade to get to know her passions and how she manages to juggle it all.
at once! Yet, I think that many, if not all of them, share common features, i.e. cell death, inflammation, mitochondrial dysfunction, blood-brain barrier dysfunction, protein-misfolding, etc. Thus, if you study a pathophysiological phenomenon in one, it is very likely that it acts the same way in the other disease, just at a different time frame, location, acutely or chronically. My choice of stroke, however, was probably by chance: During my Bachelors, I was still intrigued by the possibilities that stem cell therapy could offer (which I am quite pessimistic about today). I did an internship and my thesis with the group of Johannes Boltze who studied the effects of human umbilical cord blood cells and mesenchymal stem cells on stroke outcome at the then recently inaugurated Fraunhofer Institute for Cell Therapy and Immunology in Leipzig. After the internship, I chose to apply for a Master program in neurosciences and that's what brought me to Berlin. Johannes Boltze and the other lab members told me that Ulrich Dirnagl, whom you are probably all familiar with, is one of the leading scientists in stroke research. When I got accepted into the program here in Berlin, I decided to follow this call and have ever since enjoyed working with Uli and absorbing his visionary ideas. He has been a great example to me when it comes to quality in research.
ARM: What is your main motivation behind neuroscience research? MZ: When I was twelve, I got to know more about the human body because we talked about different types of blood and stuff like that in biology classes at school. For some reason, diseases like HIV and tinnitus caught my attention. It started to get more and more fascinating when we were introduced to the world of genetics. At that time, the hype around stem cells started and I wrote a term paper debating the chances of stem cells for therapy. At some point, I decided that I wanted to do research to figure out new therapies to cure untreatable diseases. And this still is my main motivation for research. I chose Biology, Mathematics, and French as my advanced courses during the last You certainly took away two years of school, even though I went a lot from this program. to a grammar school specializing in lan- But you will leave Berguages – that’s why I can speak French lin to do your postdoc in and Italian, too! I never really liked bot- the US. What is it that any or zoology because I hated to learn draws you away? things by rote – I wanted to understand Well, without a doubt, Berthings! So, genetics was my favorite. But lin is great and I learned a then, during the last term at school, I got lot here. However, after to learn all about the mysteries of neuro- six years, of which I spent five in the same science and the brain and there was no lab (1-year Master thesis and PhD), I think looking back! it is time to move on. I want to face new challenges, learn something new, and What is your topic of research? develop my own research theme – basiI do stroke research. A lot of people cally, I want to bring myself to the next asked me why I chose stroke over Al- level. I guess you should move to a difzheimer’s, Parkinson’s or any other dis- ferent environment after the PhD to get ease. Of course, there are many diseases to know how other people work, also in of the nervous system we don’t know terms of leadership and teamwork. And much about. But you can’t study them all you should broaden your network. Only 2014 International Graduate Program Medical Neurosciences
then will you be able to build your own ideas and research group. I hope I will find all this at my new home. I will work with Rajiv Ratan at Burke Medical Research Institute (affiliated with Weill Medical College of Cornell University) in White Plains, NY. I will continue to work in stroke research, but going back to a more biological question rather than the very methodology-based imaging. I also shift to the recovery side of the disease and to hemorrhagic stroke. Now to something less research oriented. What motivated you to revive the newsletter? In February 2010, Lutz, the program coordinator, sent around an email asking for contributors to revive the CNS newsletter. As I had been writing for youth magazines before, I thought this would be a great opportunity for me to improve my writing skills. I also felt the need for our program to have a sort of communication tool. Together with other Master and PhD students, namely Katyayni, Julia, Nicole, Gina, and Ryan, we relaunched the newsletter in May 2010. Lutz gave us a lot of freedom in what we wanted to write about. Ralf helped us with the first layout using LaTeX.
I have the ability of pushing people to get things done before the deadline (laughing) (editor who shall remain nameless: it’s true!!!!). Thus, during the first issues, the natural course of events led to me being responsible for getting the articles on time. At that time, nobody guessed that we were going to bring the newsletter this far. I think I can say that I am proud of how professional the newsletter looks now – an achievement by
Student Parade
CNSNewsletter September 2014
Photo: Tobias Bohm
many many enthusiastic writers, proofreaders and last, but not least, Viktoria who designs a wonderful layout and always has lots of great ideas on how to improve it.
I won a world championship in a team fight as well as three silver medals, one in individuals and two in team fight. But, you know, there are several karate federations in the world. Sadly, I was not even close to qualifying for THE world championships of the world karate federation which will take place in Bremen this November. But I guess those karate
in other cities and with other migrant backgrounds in Germany. Therefore, we developed an umbrella organization, the Schülerpaten Dachverband e.V., with which we want to expand our program. We already founded Schülerpaten organizations in three other cities in Germany. My role as the head of both organizations was mainly project management
What other passions do you have besides science? I understand you are a karate champion. How did that start? Yes, one of my greatest passions is karate. I think I always wanted to do Karate “I am a workaholic” as I was inspired by the movie Karate Kid (smiling). However, I only just started karate in the second year of my Masters, champions started when they were 10 – again pushing people forward – and almost five years ago now. From the first and train at least 5-7 times a week. strategic development of the organizalesson on, I was addicted to it. Now, I tion. wear the brown belt and train 3-4 times Congratulations! Your achievements a week. are fantastic. You certainly do not PhD, publication pressure, karate, The karate I do is however not the have to hide your light under a bushSchülerpaten, newsletter – if your day traditional Shotokan. I train in Modern el. Apart from sports, I know that also has 24 hours, please answer the Sports Karate, i.e. a form of karate fo- you were also involved in starting million $ question as to how you mancused on sports fighting. We omit all the an NGO. What is the goal of Schülerage to find the time for everything? traditional rituals. We train in our native paten? Some people say that I have a twin – language, not Japanese. But most impor- Children and teenagers with migrant which is of course not true (laughing). tantly, we use a special didactics to learn backgrounds often need tutoring in I am just extremely passionate about all the techniques. It is called the retroad- order to achieve higher grades and in- what I do. I just love it. And I love to see ditive method and helps you learn tech- crease their potential in school, but things growing and to help other people. niques very fast. Modern Sports Karate is their families cannot afford it. At the I have a lot of energy and an intense a constantly developing sport, much like same time, there is an enormous poten- but short sleep. I wake up early and do science, as we continuously learn about tial to engage in volunteer work among things. I regain energy by all the good more effective techniques and tactics university students all across Germany. things that happen and knowing that I for sports fighting. This is very much This is where Schülerpaten comes into am part of it. Maybe, I am a workaholmy style – not obeying rules that do not play: We bring together volunteers and ic. But I enjoy doing all this stuff, so it make sense. children with migrant backgrounds by doesn’t trouble me much. Karate or the way we train in it, is also establishing one-on-one mentorships. a sport in which you can develop yourself By tutoring individually at the children’s Just a final question: Have you ever at any time, even if it follows a satura- homes, we promote an exchange be- doubted your career as a scientist? tion curve where it becomes harder the tween different cultures and better edu- There is an Italian song that goes like better you become. And it is competitive. cational opportunities to foster integra- this: “Il primo amore non si scorda mai.” Those two characteristics fit my person- tion and mutual understanding. We offer This means that the first love is what you ality very well. You have to have a strong supervision, seminars and extracurricu- never forget. Follow your destiny, your will, intrinsic motivation, and the will to lar events for our matches to gain last- passion! improve yourself if you want to become ing experiences together. a black belt (which is still by the way not Together with friends of mine, we Thank you, Marietta! We wish you all the the end!). started our project in Berlin, where best for your postdoc! Schülerpaten Berlin was founded in Sounds like you found your perfect 2009. Today, about 30 volunteers are balance to science. But you haven’t part of the organizing team. Since told us about the championship you the beginning of the project, we have won. This is not a myth, is it? brought more than 350 mentorships Fortunately, it is true (smiling modest- between German volunteers and Arab Apoorva Rajiv Madipakkam, ly)! Last year in March in Verona, Italy, children into being. when I was still wearing the blue belt, We want to reproduce our success PhD student, AG Sterzer www.medical-neurosciences.de
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CNSNewsletter September 2014
Tracing the Roots of Aggression
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any evolutionary theories explain the development of human aggression as a necessary trait for survival. However, aggression rarely has practical use in contemporary society. When exhibited, it is often in a violent and illegal context and therefore it is incriminated. Sometimes, it can even be considered part of someone’s temperament. Aggression is thought to be the result of a complex corticolimbic interaction between subcortical neural systems, decision-making circuits, and frontoparietal regions [1]. Strong genetic and hormonal influences, in addition to the various environmental stimuli, seem to regulate these networks. This raises questions regarding the degree of responsibility that violent people bear.
Aggression Is a Male Phenomenon According to statistics, the ratio of crimes committed by males compared to females is greater than 10:1. The more aggressive behavior of males starts to manifest itself even before adolescence, with boys being more likely to be involved in some kind of antisocial conduct [2]. Hormones are among the first suspects for male aggression. Exposure to androgens in the early stages of adolescence is thought to constitute a possible cause. However, according to a recent meta-analysis, the association between testosterone levels and antisocial behavior is weak [3]. Next is the stress hormone cortisol, whose action is regulated through the hypothalamus and adrenal axis. Lower cortisol concentration was found in the saliva of males with antisocial conduct [4]. Finally, low levels of the serotonin metabolite 5-HIAA and low blood sugar are other messengers implicated in the regulation of aggressive behavior. Is It You Y? More than four decades have passed since males with XYY syndrome, known also as supermales, were associated with criminal behavior. A higher percentage of XYY men was found in prisons and in institutions for criminally insane people than was found among the normal population. This hypothesis has been significantly weakened after the publication of epidemiological studies that suggested otherwise [5], although it has not been totally refuted as emerging evidence still supports the initial claim [6]. Taking a closer look at the genes, recent knockout studies in mice have excluded any contribution of the Y-linked loci to aggression [7]. Nevertheless, the investigation of other chromosome loci revealed genes that might explain the sex-related difference in aggression and should be interpreted along with the hormone hypothesis. A shorter GAG repeat in the Androgen receptor in Swedish and Indian males accused of aggressive behavior has been associated with it [8]. Certain polymorphisms of the monoamine oxidase (MAOA, MAOB)coding genes have been linked with functional differences in expression. A plethora of enzyme-coding genes (COMT, dopamine-β-hydroxylase and tryptophan hydroxylase) has been linked to male aggressive behavior [9]. Environmental Interactions Stressful events, especially in the first years of life, confer a higher risk for manifesting antisocial conduct. Interestingly, it seems that stress triggers aggressive behavior in males with a “vulnerable” genetic background and more specifically a low-activity polymorphism in the MAOA gene. The causality in this case is not clear yet, as evidence suggests 2014 International Graduate Program Medical Neurosciences
that an initial stressful event down-regulated the activity of the MAOA genes later on [2]. The Role of Recreational Substances Substance use is closely related to offending behavior in both sexes, with alcohol being the most common culprit. It is not only widespread alcohol use, but also its high correlation with violent behavior that make it one of the most significant perpetrators of aggression. Drug users on the other hand, rarely exhibit such behavior, with cocaine users being the only exception [10]. Aggressive behavior, like every behavior, is difficult to approach and explain with molecular and genetic mechanisms. However, there seems to be a notable interaction between the environment and one’s genetic background. This requires further investigation, as the potential implications for preventing the development of an aggressive behavior, even in a small portion of the population, could improve dramatically the fabric of our societies.
Source: Andreas A. Diamantaras
[ 1] Coccaro et al, Biol Psychiatry, 2011 [2] Craig and Halton, Hum Genet, 2009 [3] Book et al, Aggress Violent Behav, 2001 [4] Shirtcliff et al, Dev Psychopathol, 2005 [5] Noël et al, Clin Genet, 1974 [6] Stochholm et al, BMJ Open, 2012 [7] Gatewook et al, J Neurosci, 2006 [8] Rajender et al, Int J Legal Med, 2008 [9] Pavlov et al, J Appl Genetics, 2012 [10] Lammers et al, Tijdschr Psychiatr, 2014
Andreas A. Diamantaras, MSc student
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Family Shapes Susceptibility to Drug Abuse
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hat both genes and environment play a role in addiction has been known for decades. But the same environmental factors can have a different influence on people based on their genotypes. In 1981, Cloninger and colleagues evaluated persons with and without genetic risk for either Type I alcoholism (mild abuse and passive-dependent character traits) or Type II alcoholism (early onset, violence, and criminality). The genetic risk factor defines a family history of alcohol abuse. Individuals with genetic risk factors more often develop alcoholism, which holds true for both types. On the other hand, growing up in a high-risk environment leads to a more pronounced effect for Type I alcoholism, but not for Type II [1]. In Swedish studies of both siblings and cousins, they found strong environmental dependency for drug abuse. Their drug abuse was more similar when they were close in age and grew up in close geographical proximity to each other. Also, an older addicted sibling or cousin conveys a stronger risk for drug abuse than a younger one. These effects were more profound when the drug abuser was male, independent of the gender of the sibling or cousin [2]. Risks of drug abuse by the mother during pregnancy are known. A recent review summarizes prenatal effects of alcohol, nicotine, cannabinoid, cocaine, and morphine abuse. Not only maternal but also paternal drug abuse cause transmissible epigenetic changes. These changes result in profound alterations to the physiology and behaviour of offspring. The phenotype persists in second generations. This indicates an epigenetic rather than a genetic cause [3].
Source: avewa-je-me, Deviantart.com, http://bit.ly/1kvGEjX
[ 1] Cloninger et al, Arch Gen Psychiatry, 1981 [2] Kendler, Ohlsson et al, Psychol Med, Jan 2014 [3] Vassoler et al, Neuropharmacology, 2014
Judith Houtman, PhD student, AG Heppner
Let Kids Be Kids
What Underlies the Rise of Food Allergies in Children?
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ood allergies are an increasing problem in Europe and elsewhere, with approximately 5 % of children under 18 in developed countries suffering from them. During the last decades, severe reactions to food have become even more prevalent. These reactions essentially result from misdirected immune responses, which somehow recognize innocuous substances as potential threats and launch an intensive assault [1]. Food allergies are usually associated with other forms of allergic sensitization. Therefore, it is likely that many risk factors are common to many subtypes of them. So far, several genes have been investigated, notably those within the cytokine cluster on chromosome 5q31 [2]. Although early population studies demonstrated that first degree relatives of affected patients showed significantly higher risk of allergy than the general populace, only a few studies have investigated the association between genetic traits and susceptibility to food allergies. However, we have a problem. Genetic changes need hundreds of years to cause diseases, and cannot, therefore, fully account for the current increase. From an environmental perspective (the ‘Hygiene hypothesis’), improved hygiene interrupts the normal development of the immune system by
removing exposure to “dirty” factors like parasites or viruses. This change leads to an increase in allergies [3]. A modified version is called the ‘microbiota hypothesis’. It states that reduced infant gut microbiota diversity is associated with allergic disease later in childhood [4]. The management of early sensitization and symptoms of food allergies is crucial, since children exhibiting signs of food allergy in early life usually go on to develop allergyrelated respiratory diseases. Therefore, parents should pay close attention to the importance of exposing their children to a wide variety of stimuli early in life. Better a strong and dirty immune system than a sanitary and shaky one! Let kids be kids, and make all the mess they want! [ 1] Herz, J Pediatr Gastroenterol Nutr, 2008 [2] Cochrane et al, Allergy, 2009 [3] Bach, Cell Immunol, 2005 [4] Azad et al, Allergy Asthma Clin Immunol, 2013
Tian Zhang, PhD student, AG Meisel www.medical-neurosciences.de
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Death in a Bottle
What the Chemical Industry Doesn’t Want You to Know
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t all started on a really beautiful day. When my first child was born, one of our visitors was quick to advise us on our newborn’s safety: “You will of course use only glass bottles and BPA-free plastic products with your child, right?” I had already heard of the ongoing debate about endocrine disruptors, but my knowledge about it didn’t amount to much. The scientist in me needed more facts than that! And as my partner was quick in adopting this “plasticfree” behavior, I was eager to understand if this craze was based on actual facts.
What Are Endocrine Disruptors? Endocrine disruptors are chemicals that, at certain doses, can interfere with the endocrine (or hormonal) system. Basically, any system in the body which is controlled by hormones can be derailed by endocrine disruptors. Since hormones control many body functions, endocrine disruptors can produce adverse developmental, reproductive, neurological, and immune effects. The list of potential adverse effects is therefore quite long and is regularly growing [1]. As hormones function at infinitesimal concentrations (in the part per billion range), endocrine disruption can occur from low-dose exposure. A bibliographic research quickly revealed that the relationship between exposures to chemicals and health effects is rather complex. It is indeed difficult to link a particular chemical with a specific health effect. Exposed adults may not show any symptoms, but the effects become striking on fetuses and embryos, whose growth and development are highly controlled by the endocrine system. Exposed subjects can suffer subtle or obvious lifelong health and/or reproductive abnormalities [2]. Effects of High Exposure The effects on adults become obvious in the case of high doses exposures, luckily a relatively rare event. Among the known cases is the dioxin event. It took place in Seveso, Italy, and is probably the most documented, at least for the long term effects on the population. On a quiet July day in 1976, following a disas-
trous incident at a local chemical plant, a cloud containing about 30 kilograms of dioxin rose in the air. The exposure of the local population was linked to devastating effects including cancers, endometriosis, and altered immune function. Symptoms sometime took decades to appear [3]. Still today, life-long immune system problems continue as subjects display a lowered ability to resist disease. But as Paracelsus famously said “the
dose makes the poison” and one major objection to the theory of endocrine disruptors is the dosage effect. Some scientists claim that there is a large gap between the high exposures seen in a laboratory experiment and the relatively low levels found in the environment [4]. However, this does not take into account the fact that endocrine disruptors can have a synergistic effect, amplifying each other’s impact. Such synergistic effects have been demonstrated at low concentrations in amphibians [5]. But since it remains unclear whether it is mediated by the endocrine system, it is not clear if such a synergistic effect might be possible in humans. A Hidden Threat How exposed are we, exactly? I was amazed to discover that endocrine disruptors are basically everywhere. They are in thermal receipts that come out of restaurants, retailers, grocery stores, and gas stations. They are in canned foods, cosmetics, plastics, and food packaging. They are in furniture, clothing, paints, varnishes and lacquers. The
2014 International Graduate Program Medical Neurosciences
list is surprisingly long. If you tested your own blood or urine, you would surely find them there. Contamination with the phthalate BPA for example is so widespread that it has been found in 95 % of the people tested [6]! The current statement of regulatory agencies is that it is difficult to show that endocrine disruptors cause human diseases. They recommend that the precautionary principle should be followed [7]. In 2013, the WHO and the United Nations Environment Programme released a study calling for more research to fully understand the associations between endocrine disruptors and the risks to health. One of the conclusions of the study pointed out that known endocrine disruptors are only the ‘tip of the iceberg’. More comprehensive testing methods are required to identify other possible endocrine disruptors, their sources, and routes of exposure. What Can We Do? Yes, there are uncertainties. But most scientists working on endocrine disruptors are already taking steps to protect their families. Most of them have stopped buying canned food. They avoid microwaving in plastic or pouring boiling water into plastic containers, even if those are labeled BPA-free. And they refuse receipts whenever they can. Concerning the health of my family, I need to admit that avoiding plastic products had an immediate and unexpected positive effect on my mood. Agreeing with my partner worked wonders for my relationship. [ 1] Frye et al, J Neuroendocrinol, 2012 [2] Colborn et al, Human and Ecological Risk Assessment, 2007 [3] Warner et al, Environ Health Perspect, 2002 [4] Vandenberg et al, Endocr Rev, 2009 [5] Hayes et al, Environ Health Perspect, 2006 [6] Wolstenholme et al, Horm Behav, 2011 [7] Diamanti-Kandarakis et al, Endocr Rev, 2009
Vieri Failli, postdoctoral researcher, AG Schwab
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CNSNewsletter September 2014
The Development of Taste Preferences
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ave you ever thought that your liking of strawberries and your resentment of cauliflower could be the result of very careful genetic programming? Besides our genetic inclination, gastronomic stimuli, starting as early as the 8th gestational week, can shape the taste preferences that we develop later in life.
Such a Sweet Tooth… Indeed, all humans seem to have encoded in their genome a preference or aversion for specific tastes that were related, from an evolutionary perspective, to increased chances of survival. An innate liking for sweets is evident in all newborns ensuring the acceptance of maternal milk. One mechanism behind this affection is the upregulation of the production of endogenous opioids. They change the perception of pain and mimic the effects of drugs in the brain. It is no coincidence
Amniotic fluid is our first food stimulus then that sucrose-containing solutions are used as analgesics for painful procedures in neonates [1]. As we grow, other endogenous factors, like polymorphisms in the sweet taste receptors (TAS1R2, TAS1R3), come into play and influence our inclination towards sweets.
Likewise, the innate aversion towards bitter foods follows the fact that most toxic substances taste bitter [2]. A Restaurant in the Womb Learning, in the form of repeated exposure to certain foods, is another individual factor influencing our taste preferences and in the end our eating habits. Our first exposure to food flavors takes place inside the womb. Flavor components pass from the mother’s blood to the amniotic fluid. Breast milk is the next, perhaps even more important, milestone. Changing its flavor according to the maternal diet provides a variety of flavor stimuli for the infant that prepares and familiarizes it for solid food [3]. However, it is never too late to influence our food preferences by regularly “training our palate”. Influencing our food preferences appropriately from the first years of life can aid in the prevention of a plethora of diseases, from cancer to obesity and diabetes, which are closely related to our dietary habits. [ 1] Ventura and Worobey, Curr Biol, 2013 [2] Ventura and Mennella, Curr Opin Clin Nutr Metab Care, 2011 [3] Beauchamp and Mennella, J Pediatr Gastroenterol Nutr, 2009
Andreas A. Diamantaras, MSc student
Environment and Genetics in Autism
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s a phenotypically and pathophysiologically heterogenous neurodevelopmental disorder, autism is a typical example of how genes and surroundings interact to produce illness. Having a child suffering from autism often brings anxiety to parents and relatives. This is because, by definition, it is a pervasive childhood disorder that affects most (if not all) domains of life. Unfortunately, this desperation, combined with being a common disorder, exposes autism to false claims based on non-existent or fabricated research. Scientists have now refuted claims that interpersonally distant parents, fungal infections, or vaccinations cause autism. However, not all environmental theories are pseudoscience. Exposure to other environmental factors, such as ethanol or rubella (particularly during pregnancy), contributes to the development of autism [1]. Several observations, derived from twin and family studies, indicate that the pathogenesis of autism also involves genetics. In most cases, autism is a multifactorial disorder that cannot be traced back to a single underlying abnormality. However, in up to 40 % of cases, the disease is caused by a single genetic mutation, for which many potential foci exist [2]. In this context, autism typically manifests as part of a broader syndrome such as tuberous sclerosis, fragile X syndrome, or phenylketonuria. Because of this strong genetic
link, a thorough genetic evaluation is recommended for all individuals with a clinical diagnosis of autism [3]. Some experts have suggested that the way autism is diagnosed itself impairs our ability to understand the condition. The main resource used for this purpose – the Diagnostic and
Genes and environment interact in autism Statistical Manual of Mental Disorders (DSM) – is based on detecting groups of symptoms rather than finding a particular etiology. Thus, our excessive reliance on the DSM may make it difficult to isolate the roles of genetic and environmental factors in the pathogenesis of the disorder by grouping disorders which seem similar but are biologically distinct. [ 1] Rodier, Sci Am, 2000 [2] Folstein, Int Rev Psychiatry, 1999 [3] Schaefer and Mendelsohn, Genet Med, 2008
Ahmed Khalil, MSc student, Erasmus Mundus Neurasmus
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How to Overcome Your Fate
Dementia is Predictable, But Not Inevitable
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ementia is the future leading health problem in the aging populations of developed countries. For most conditions leading to dementia, a genetic basis is proposed, but there’s a good chance that these can be overcome by leading a healthy lifestyle.
depression-induced pseudo-dementia features similar symptoms [2]. These diseases have diverse causes, some of which are very clear (WKS: vitamin B1 malnutrition; HD: poly-glutamine repeats; LBD: accumulating alpha-synuclein; NPH: blockage of cerebral spinal fluid flow, CJD: infectious misfolded proteins; CTE: repeated head trauma), which may or may not be treated and/ or simply avoided. In others (AD and PD), the underlying mechanisms are poorly understood, although they are subject to intense research (see also “Under-
tosomal dominant mutations (partially matching genes affected in PD) are known for FTD. They eventually cause regional brain degeneration of the frontotemporal lobe [3].
Dementia due to Non-Genetic Factors Genetic influences on dementia progresA Disease of Modern Times sion, however, do not solely explain its In modern societies, improvements in cause. Age alone is accompanied with healthcare and general nutrient availmild cognitive decline. Yet there are othability have allowed people to reach the er conditions impairing cognition with highest life expectancies ever known to even less of a genetic background. man. This is a steadily increasing trend, A very intriguing example is depression-induced pseudo-dementia. Although aged people quite often present Dementia is not a fate which cannot be overcome with depressive symptoms, the typical observed for many decades now. How- standing the Pathogenesis of Parkin- dementia symptoms of memory defiever, reaching an evolutionarily unprec- son’s Disease” on the right). cits, impaired executive function, and edented age confronts the biochemical Genetics Partially Determine processing speed as well as speech and machines that our bodies are with un- Dementias language deficits can also be found in foreseen challenges. Together with cur- HD and other poly-glutamine diseases individuals much younger and without rent standards of living, old age leads to ultimately arise from autosomal domi- pathological evidence (e.g. amylopathies, several health problems such as cancer, nant inheritance of nucleotide repeats, tauopathies, brain atrophy and the like). cardiovascular disease, and dementia. thus being the most obvious example This is because they are experiencing for genetically induced dementias [3], severe depression [7]. While the cogniDementias as Global Economic Bur- whereas the genetic influence in other tive deficits in depression are significant den conditions is far more subtle. in comparison to healthy, not depressed While cancer and cardiovascular disease The most often diagnosed condition controls, their symptoms appear mild are increasingly well treated, modern prior to dementia is AD. It is known to compared to “real” dementias. Luckily, medicine is still struggling with demen- be two rather independent conditions: tias, whose main risk factor is increasing Early- and late-onset AD. Early-onset AD age. Facing the generally aging popula- affects people aged 30 to 50 years from A healthy mind lives in a tion due to low birth rates together with a few families bearing highly penetrant healthy body large population cohorts such as the mutations of the amyloid precursor pro“baby boomers” reaching their seven- tein (APP) or presenilin 1 and 2 genes ties, care requirements for demented (PSEN1 and PSEN2). upon successful treatment of the deprespatients are going to be the highest soFor late-onset AD, the main risk fac- sion cognitive function is restored [7]. cioeconomic burden to modern societ- tor is age. It affects people aged 70 and Other non-genetic factors increasies [1]. beyond. Several genes or gene variants ing the risk of dementia arise from daily are known to be associated with the living. A multitude of twin studies have Dementia as Endpoint of Various disease. They are involved in Aβ me- identified prominent risk factors for Diseases tabolism, gene expression, posttransla- dementia: Obesity and overweight, hyThe term dementia comprises deficits in tional modification, microglial function, pertension, diabetes, dyslipidemia, little cognitive, emotional, and social abilities cytoskeletal function, axonal transport, physical activity, low levels of education, which impair activities of daily living. hippocampal synaptic function, cell sig- and little social engagement [8,9,11]. InHowever, it only denotes a clinical state naling, inflammatory response, and lipid terestingly, low quality and quantity of that is the final stage of a wide range of metabolism. Yet, none of them alone sleep were found to increase Aβ accumuunderlying pathologies. Diseases even- causes AD [4]. lation, which in turn negatively affects tually causing dementia include, but are Further associations with AD were sleep – a vicious cycle accelerating AD not limited to: Alzheimer’s Disease (AD), found concerning several hypermethyl- progression [10]. Parkinson’s Disease (PD), frontotempo- ated, thus down-regulated, genes (see ral lobar degeneration (FTD), Hunting- also “Lamarck’s Last Laugh: The Nur- Genetics Can Be Partially Overcome ton’s Disease (HD), Lewy Body Dementia ture Within Your Genome” on pp. 2) [5]. And yet, there is hope! Most risk factors (LBD), Creuzfeldt-Jacob Disease (CJD) The most commonly known may be the can be avoided by adopting a healthy and other prion dementias, vascular de- epsilon 4-allele of the apolipoprotein lifestyle, even when starting only in midmentia (VaD), Wernicke-Korsakoff-Syn- E gene (APOE). It is a well-established life [12]. Twin studies have shown that drome (WKS), normal pressure hydro- genetic risk factor, but it probably only healthy living may diminish the influence cephalus (NPH), and chronic traumatic plays a role in women [6]. of genetic risk factors. In particular, the encephalopathy (CTE). Although very FTD is the most frequent dementia reduction of vascular risk factors reducdifferent from those “real” dementias, after AD. A number of unrelated, au- es the development of dementia, inde2014 International Graduate Program Medical Neurosciences
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pendent of its cause. Achieving a reduc- ments are possible. For example, it was tion of vascular risk factors by combining found that stress levels influence the healthy (Mediterranean) diet with physi- age of disease onset [11]. cal activity is especially effective [9]. The general observation that high lev- Mens Sana in Corpore Sano els of education, cognitive flexibility, and A healthy mind lives in a healthy body. social activity go along with a lower risk Modern medicine increasingly proves for dementia is referred to as “cognitive this Roman proverb correct. A group of reserve”. It describes superior cognitive international researchers at the Internaabilities upon equal physiological state tional Conference on Nutrition and the [9]. Even in such a seemingly predeter- Brain 2013 in Washington formulated mined disease like HD, certain improve- guidelines for AD disease prevention, as
Guidelines for AD Prevention (International Conference on Nutrition and the Brain 2013, Washington, D.C., USA) 1. Avoid saturated fats and trans-fatty acids, found in dairy products, snack pastries, and fried food. 2. Choose a healthy diet mainly consisting of vegetables, legumes, fruit, and whole grain products. 3. Satisfy vitamin and micronutrient demands (esp. vitamin E) from healthy foods, not supplements. 4. Satisfy demands in B12 from foods and, if needed or when over 50 years, foods enriched in B12. 5. Avoid excessive aluminum, iron, and copper intake (e.g. from supplements). 6. Incorporate aerobic exercise into your daily living. 7. Ensure 7-8 hours of sleep daily and treat sleep disorders (e.g. obstructive sleep apnea). 8. Ensure mental and social activity of at least 30 min a day.
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shown in the box. These are actually applicable to most pathologies leading to dementia [12]. Given that all this advice accounts for healthy living anyway, it appears as a cheap investment into not just a long life compared to centuries ago, but a long and healthy life preserving what makes us the people we are. [ 1] Gillette-Guyonnet et al, Br J Clin Pharmacol, 2013 [2] http://www.alzinfo.org [3] Paulsen and Igo, Semin Neurol, 2011 [4] Zou Z et al, Biomed Res Int, 2014 [5] Sanchez-Mut et al, Brain, 2013 [6] Altmann et al, Ann Neurol, 2014 [7] Kang H et al, Ann Indian Acad Neurol, 2014 [8] Xu WL et al, Neurology, 2011 [9] Middleton and Yaffee, Arch Neurol, 2009 [10] Ju et al, Nat Rev Neurol, 2014 [11] Mo et al, Neurobiol Dis, 2014 [12] Barnard et al, Neurobiol Aging, 2014 Picture Source: sanguinie, Flickr, http://bit.ly/1rVsJT9
Bettina Schmerl, MSc Medical Neurosciences
Understanding the Pathogenesis of Parkinson’s Disease
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arkinson’s Disease (PD) is one of the most common degenerative disorders in older adults. It is characterized by a host of motor and cognitive effects. Yet, for all that we know about it, there are still many mysteries that make its exact pathogenesis unclear. How might nature and nurture interact to give rise to this devastating condition?
Genetic Predisposition, Great and Small We’ll start with nature, where a small number of mutations have been linked to the disease. Among them are genes coding for proteins such as alpha syn-nuclein and leucine-rich repeat kinase 2 [1,2]. The former has an important role in formation of Lewy bodies, while the latter targets proteins for degradation [1]. Understandably, these mutations can wreak havoc on neurons, but may not be the only culprits. Several large genome-wide association studies have identified many other alleles that may have a cumulative role in PD [1,2]. Case closed? Despite the strength of these findings, they only account for about 15 % of patients worldwide [3]. What else might be going on? The Not-so-great Outdoors The vast number of PD cases are idiopathic, with no discernable cause. However, several risk factors have been welldocumented. Primarily, exposure to pesticides seems to be important, as does “rural living” [3,4]. Other studies have also suggested that factors such as drinking well water, head injuries, or being male may also have a small effect [3]. Yet, the story is far from complete. Scientific consensus must, for now, rest on an interplay of genes and environment.
What about prevention? Chances are, you’re already hard at work. Caffeine has been shown to lower risk, with the benefit increasing linearly with consumption [3,5]. Surprisingly, smokers have also been found to be at lower risk for PD than the general population [3,6]! Ultimately, the exact contributions of nature and nurture in PD are unknown. The best that we can do for now? Have a coffee, maybe some nicotine gum, and get back to work in the lab!
Source: wikimedia commons, http://bit.ly/1uXZJzA
[ 1] Lesage et al, Hum Mol Genet, 2009 [2] Lester et al, Neurologist, 2006 [3] De Lau et al, Lancet Neurology, 2006 [4] Gorell et al, Neurology, 1998 [5] Prediger, J Alz Dis, 2010 [6] Quik et al, Biochem Pharmacol, 2009
Constance Holman, MSc student www.medical-neurosciences.de
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Giving Birth to Epilepsy
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pilepsy is a heterogeneous group of seizure disorders. It is considered to be familial and genetically influenced, but in most cases, the exact cause is unknown and attributed to multifactorial inheritance.
The Biological Component Significant progress in identifying genes that are associated with increased risk of epilepsy has been made during the last
The heritability of epilepsy can be up to 88 % decades. This progress was based on epilepsies that are inherited following the Mendelian laws. However, single gene mutations are solely responsible for the genesis of epileptic activity in only about 1 % of all epilepsies. The remainder are considered to be idiopathic or to follow a complex inheritance [1]. The Twins’ Hypothesis As the cause for the majority of epilepsies remains unknown, researchers have used twin studies to estimate the contribution of the environment to the genesis of epilepsy. Twin studies compare the occurrence of a disease among monozygotic (MZ) and dizygotic (DZ) twins.
In a Danish cohort of 11,900 twin pairs, the rate of concordance (i.e. the percentage of twin pairs in which both twins are affected) among MZ twins was 37 % compared to 8 % in DZ twins. According to an etiology analysis, the heritability of epilepsy (i.e. the percentage of different phenotypes attributable to genes) was 70 % and 88 % in the younger and older group of twins respectively. The remaining percentage represents the influence of environmental factors [2]. Another twin study in Australia found 65 % and 18 % concordant pairs in MZ and DZ twin respectively. Nevertheless, they noted that this percentage was higher in cases with generalized compared to partial epilepsy [3]. So far, the evidence from twin studies does not suggest the implication of specific genetic loci, but rather the presence of a multifactorial etiology. Efforts to identify further high-risk genetic loci have thus far been fruitless, indicating that epileptic disorders are characterized by great genetic heterogeneity. This might partially explain why the majority of them are classified as idiopathic. [ 1] Ottman et al, Jasper's Basic Mechanisms of the Epilepsies, 2012 [2] Kjeldsen et al, Epilepsy Res, 2002 [3] Berkovic et al, Ann Neurol, 1998
Andreas A. Diamantaras, MSc student
The Perpetrator of Schizophrenia
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chizophrenia is perhaps the psychiatric disorder in which the contribution of environmental and genetic factors is the hardest to distinguish. According to the current knowledge, environmental factors act upon a predisposed genetic background leading to the development of the disease. But is this always the case?
The Schizophrenic Gene The higher occurrence of schizophrenia within families is a well-known observation, and the genetic contribution to the disorder has been confirmed using twin studies. Evidence points to a concordance rate of about 50 % among mono-
Schizophrenia is a multifactorial/ polygenic disease with 80 % heritability zygotic twins. Since then, genetic linkage studies have been able to locate two chromosomal regions, 8p21–22 and 22q11– 12, that are closely associated with schizophrenia. The studies, however, lacked precision and could not specifically define the implicated genes [1]. Genetic association studies, in turn, compare gene variations among individuals. They have identified specific genes that code proteins that participate in the pathophysiology of schizophrenia, like dopamine and glutamate receptor genes [2]. The current opinion is that schizophrenia is a multifactorial/polygenic disease with high heritability (around 80 %) [3].
2014 International Graduate Program Medical Neurosciences
Environment Has Its Role Norwegian immigrants back in 1932 provided the first clue for the role of the environment in the development of schizophrenia. The occurrence of the disease among them was noted to be higher as compared to the occurrence in their homeland [4]. Compelling evidence suggests the role of environmental factors in the manifestation of schizophrenia. For instance, a higher risk of the disease occurs in children whose mothers had an infection during pregnancy, in those who were born during winter, who experienced childhood trauma, or who were adopted by families with a history of schizophrenia [3]. Additionally, stressful life events and cannabis consumption are a common trigger for schizophrenia in adolescence. Gaps in the knowledge for the link between genes and environment leave burning questions unanswered. Do different types of schizophrenia emerge when genetic or environmental factors predominate? And is any of these two factors sufficient by itself to trigger the disease? [ 1] Lewis et al, Am J Hum Genet, 2003 [2] Duan et al, Hum Hered, 2007 [3] Tandon, Keshavan et al, Schizophr Res, 2008 [4] Odegaard, Acta Psychiatr Neurol Scand, 1932
Andreas A. Diamantaras, MSc student
Dr. Harebrained & Check This Out
CNSNewsletter September 2014
Neuroscience in Your Everyday Life Why Is It Again That We Cry When We Are Sad?
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he mystery of shedding tears has intrigued mankind for a while, most notably amongst them, Charles Darwin. He concluded back in 1872 that “Englishmen rarely cry, except under the pressure of the most acute grief; whereas in some parts of the continent men shed tears much more readily and freely” [1]. Is crying when we are sad an evolutionary conserved mechanism, universal across cultures? There are a number of indications pointing to this. Most scientists agree that the underlying psychological cause for crying is “perceived helplessness”. However, we still hope and rely on the fact that someone will help us. Depressed people on the other hand rarely cry because they believe no one will be able or willing to help them. This is also a hypothesis for why severely neglected infants stop crying [2]. In neonates, crying is an inborn mechanism thought to trigger caretaking behavior in parents and induce bonding, the so-called attachment theory. This, of course, transfers into adulthood, where crying is seen as an attachment/ separation behavior [3]. All in all, tears serve to communicate an emotional message. Interestingly, this is not only at the psychological level,
but also at the biological level where they are thought to incorporate a chemosignal. This is still a fairly new field. One study claimed that when men sniffed female negative-emotion-related odorless tears, they were less sexually aroused [4]. But I hope this is not the only biochemical signal that will be found in tears. [ 1] Darwin, “The expression of the emotions in man and animals”, 1872 [2] Miceli and Castelfranchi, New Ideas Psychol, 2003 [3] Nelson, Clin Soc Work, 1998 [4] Gelstein et al, Science, 2011 Do you also sometimes wonder about the simple neuroscientific questions in everyday life, but don’t really feel like looking them up right away? For questions like this, just mail us your question (
[email protected]) and Dr. Harebrained will give us his explanation in the next issue! Our next issues question: Why is it again that we forget?
Veronika Lang, PhD student, AG Kramer
Research Assessment Without Journal Impact Factor
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worldwide and cross-disciplinary initiative started by the American Society for Cell Biology is trying to improve the assessment of quality in science. Alternative measurements to the journal impact factor are highly desirable. Here is an excerpt from the San Francisco Declaration on Research Assessment (DORA): “The Journal Impact Factor is frequently used as the primary parameter with which to compare the scientific output of individuals and institutions. The Journal Impact Factor, as calculated by Thomson Reuters, was originally created as a tool to help librarians identify journals to purchase, not as a measure of the scientific quality of research in an article. With that in mind, it is critical to understand that the Journal Impact Factor has a number of well-documented deficiencies as a tool for research assessment. These limitations include: A) citation distributions within journals are highly skewed [1–3]; B) the properties of the Journal Impact Factor are fieldspecific: it is a composite of multiple, highly diverse article types, including primary research papers and reviews [1, 4]; C) Journal Impact Factors can be manipulated (or “gamed”) by editorial policy [5]; and D) data used to calculate the Journal Impact Factors are neither transparent nor openly available to the public [4, 6, 7].”
They make one general and 17 specific recommendations. Their general recommendation is: “Do not use journal-based metrics, such as Journal Impact Factors, as a surrogate measure of the quality of individual research articles, to assess an individual scientist’s contributions, or in hiring, promotion, or funding decisions”. If you want to know more and sign the declaration, check it out: http://am.ascb.org/dora/
[ 1] Adler et al, Citation statistics. A report from the International Mathematical Union, 2008, http://bit.ly/1rOk34i [2] Seglen, BMJ, 1997 [3] Not-so-deep impact, Nature, 435 [4] Vanclay, Impact Factor: Outdated artefact or steppingstone to journal certification, Scientometric, 2012 [5] The impact factor game, PLoS Med, 2006 [6] Rossner et al, J Cell Biol, 2007 [7] Rossner et al, J Cell Biol, 2008
Contest We are always interested in including your contributions. You can submit anything you see fit on the topic of neuroscience. Send us your most exciting microscopic pictures, or a creative photo, thoughts on neuroscience or self-written poems – whatever comes to mind! The best contribution will be published and rewarded with the book “So You Want to be a Scientist?” . So, what are you waiting for? Start the engine of your mind and get going! Trust us, it is worth participating! Send your contribution to
[email protected] to win “So You Want to be a Scientist?”. Deadline for submission for the next issue: October 31, 2014. This issue’s winner is Vieri Failli who contributed the article “Death in a Bottle”. Thank you very much for your contribution. www.medical-neurosciences.de
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Conference Report & Course Watch
CNSNewsletter September 2014
14th Annual Meeting of the Vision Sciences Society
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n the second week of May, vision scientists from around the world came together in Florida, for what is probably one of the largest vision science conferences: the Vision Sciences Society (VSS). With every possible topic concerning visual perception, from attention and face perception to computational modeling and eye movements, the conference was filled with the presentation of exciting ideas and data. Workshops that included discussions on the most controversial topic in science – journal publications and impact factors – made the conference even more lively. Apart from the daytime sessions, the evenings were also filled with interesting events like the Illusion Of The Year contest. The dynamic Ebbinghaus illusion bagged the prize for this year. The classical Ebbinghaus illusion is the apparent change in size of a central circle, depending on the context in which it is presented. That is, the central circle appears bigger when surrounded by smaller circles and smaller when surrounded by bigger circles although the actual size remains the same. The classical illusion has a new twist to it which can be checked out here: http://bit.ly/1s6cpki A report of this conference would, of course, not be complete without the Demo Night, where one could be a part of several visual illusions and phenomena. For example, there was a demonstration of the famous Beuchet chair. Here, the two separate parts of the chair seem to belong together even though they are at different distances. However, they
have the appropriate sizes to create a single image on the retina at an intermediate distance. The Demo Night felt a bit like Disneyland for scientists... it was magical, exciting, and required standing in a queue to take part in the demonstration. It definitely felt like the organizers had the perfect recipe for the balance between work and fun! Source: Peter Thompson (University of York), http://viperlibnew.york.ac.uk/ The deadline for submission of abstracts for next year’s VSS is the middle of December. For more information: www.visionsciences.org
Apoorva Rajiv Madipakkam, PhD student, AG Sterzer
Hunting for Cajal’s Butterflies
A Report about the Interneuron Summer School
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ast week of June, Amsterdam. Researchers and students continued a quest that Ramon y Cajal started more than one century ago when he first described cells with short axons, the so-called interneurons. The Netherlands Institute for Neuroscience dedicated five-day summer school to these fascinating cells. Interneurons typically release GABA and project locally or at long range. They form inhibitory networks targeting specific domains of excitatory and inhibitory neurons. Through these networks, they mediate the communication within and between brain areas by orchestrating neural oscillations. Dysfunction of interneurons is associated with the excitation/inhibition imbalance we see in epilepsy, schizophrenia, and autism. Interneurons are characterized based on properties such as morphology, connectivity, and physiology. Although a wide variety of subclasses are described, the cues that determine interneuron diversity remain unclear. The first part of the Interneuron Summer School was precisely about this. Gordon Fishell explained that this diversity originated from 1) post-mitotic interactions and 2) intrinsic programs established within the interneuron progenitors at the ganglion eminence. Interestingly, clusters from the same progenitor cells migrate to distinct brain regions and develop into different interneurons. Therefore, extrinsic signals appear to be critical during differentiation. Wnt signalling, for example, might induce somatostatin expression in the caudal portion of the medial ganglion eminence.
2014 International Graduate Program Medical Neurosciences
György Buszsáki, recipient of the Ariëns Kappers Medal spoke about hippocampal rhythms. His talk highlighted the fact that ripple oscillations are necessary for memory consolidation. These oscillations are locally generated and their frequency is determined by the interactions between parvalbumin-positive interneurons. However, direct activation of parvalbumin-positive interneurons do not induce ripples, suggesting that pyramidal cells play a critical role in their generation. All in all, the Summer School was a truly enlightening experience and is definitely recommended for anyone in this field. For more information: http:// interneurons.nin. knaw.nl/home. Parvalbumin expression (red) in hippocampal slices of rats with YFP-VGAT-positive interneurons (green), © Luisa Hasam
Luisa Hasam, PhD student, AG Kovacs
CNSNewsletter September 2014
Brain in Press & A Taste of Home
Brain in Press Human Brain Project Controversy
Europe Suffers from Academic Doping
Leaders of Europe’s Human Brain Project are under scrutiny after shifting the direction of the program for the upcoming phase. As more emphasis is given to brain simulation and computer technology, cognitive neuroscience has been excluded from the core plans of the program. Many researchers are upset by this decision and have suggested it may foreshadow the failure of the program to address key issues such as brain disease. Recently, more than 150 neuroscientists throughout Europe pledged to boycott the project until their concerns are addressed.
There has been a increase in the number of European students using what are known formally as cognitive enhancers, or “smart drugs”, to maintain competitiveness against peers. A recent Swiss study revealed that one in seven students at Swiss universities used smart drugs to enhance performance on exams. Popular substances include Ritalin and Modafinil, which are drugs that help increase attentiveness. The New York Times quotes scientists that doubt the true efficacy of these smart drugs and whether they actually improve students’ long-term learning capabilities.
Reference: Abbot, Row hits flagship brain plan, Nature, 2014, http://bit.ly/1noiimX
Reference: Dmitry Petrounin: European Students’ Use of ‘Smart Drugs’ Is Said to Rise, New York Times, 6 July 2014, http://nyti.ms/1n5BIwB
Social Conformity May Only Be Short-Term How much does exposure to others change your opinion and how long does this effect last? A research group in China tried to tackle this question by analyzing the differences in participants' ratings of the facial attractiveness of given photographs with and without an average rating provided. Their results illustrated that the influence of others’ opinions as reflected in the fictional averages lasted no more than a week, usually around three days. The group speculates that socialconformity is due to a change in personal views rather than compliance with the views of others. Reference: Huang Y et al, Psychol Sci, 2014
Crayfish Have Feelings Too A recent study has shown that crayfish experience anxiety and even respond to anti-anxiety medication. Electric shock treatment and open field tests were used with varying light conditions to assess the stress level of these crustaceans. Interestingly, light avoidance correlated with increased levels of serotonin, and this behavior was modulated by conventional human anti-anxiety medications. This research brings attention to the existence of basic emotion in an invertebrate organism often thought of as primitive. Reference: Press Association: Crayfish feel stress, claim scientists, The Guardian Online, 13 June 2014, http://bit.ly/1rSa4uM
Capsaicin Receptor May Trigger Asthma Attacks Although there are many known environmental triggers for asthma, researchers may have elucidated how these allergens are able to provoke attacks. By ablating a specific subset of neurons that send signals to the cranial nerves, scientists were able to prevent asthma attacks upon exposure to common triggers in mice. These TRPV1 containing neurons may be the pathological link between the immune and nervous systems in asthma. They are activated by a molecule, sphingosine-1-phosphate, known to be secreted in the lungs of people with asthma. Further research is necessary to see if these findings are consistent in humans. Reference: Sarah C. P. Williams, Nervous system may hold key to treating asthma attacks, Science 2014, http://bit.ly/1rRAkmB
Carla Wood, MSc student
Cat Café
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o you sometimes feel a need for coziness? A place where you can relax with a cup of coffee and homemade goodies in pleasant surroundings? For me, the perfect place for coziness can be found in Neukölln, where I really love to go when I need coffee and cuddling: Pee Pee’s Cat Café. This little café, located near “Thomashöhe”, is home to “Pelle” and “Caruso”, two male grey tabby cats that were abandoned as kittens. While watching, touching or playing with the cats, you can indulge yourself in the selection on offer. The menu includes white coffee, lots of homemade cakes, and hearty goodies for reasonable prices in a light and inviting interior. Besides an almost mandatory “Katerfrühstück” (hangover breakfast) with scrambled eggs, a baguette, and
salmon or pickled herring, they also offer vegan dishes. If you are not allergic to cats you should really try this place! Pee Pee’s Katzencafé Thomasstr. 53 12053 Berlin-Neukölln
Betty Jurek, PhD student, AG Prüß www.medical-neurosciences.de
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Short Story
CNSNewsletter September 2014
The Gift
A Short Story
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t was Isabella’s first day working as a of middle height nurse in an elderly nursing home. At and a slightly bent 7 am, she was in the garden surround- stature stood close ing the home. At her footsteps lay plenty by, watching her of plumeria flowers; they were white and impatiently. His open to the world like beautiful balleri- feeble body was innas with a tinge of yellow in the center capable of bearing adding to their thorough brightness, his weight, and he driven away by the wind just like she was leaned on a dark Source: http://www.metmuseum.org/toah/hd/dura/hd_dura.htm driven to this new place with no image of brown wooden cane. what shall follow. His deeply wrinkled A sudden breeze had followed along face disguised a mixture of joy and pain, spective of the world, it became all the in the scene of utter incomprehensibil- and his teary eyes spoke of the untold more inexplicable. She, unlike many othity. Next to her stood a magnolia tree tales of life. ers who are either unaware or careless with its flowers blossoming so elegantly He was life and death concealed in a of the matter, questioned the integrity of and lovingly. An overwhelming feeling human being. As much as life is an enig- life that is both begotten and abolished grew inside her as she stood still grasp- ma, so is death. It is the only experience with every new sunrise. Perhaps the ing the beauty instilled within the scene one cannot discover. The secret part theory of life exists in that the winds of with silence. The sun was hidden shyly of life that cannot be revealed except change seize not to blow wherever life behind clouds of anticipation of a brand to those who are indefinitely frozen in exists. And if life blossoms through the new day. It wasn’t just a job, it was a new time and banished from the cycle of life. seeds of change, then death is both the moment in her life with which she had Isabella approached the old man and means and end of life, dubiously constood remembering all the novel experi- hugged him tightly as though destiny cealed in the form of inexistence. ences in her life. The first achievement, had rejoined them once again. He was On a quiet morning in her small balthe first love, the first loss, and every her father and her only supporter in life. cony, she contemplated the person she possible beginning had struck her all at As years passed by and as much as he would love to become, like a little child once. She felt like a piece of music was felt overjoyed to watch her grow into the with invincible dreams of greatness. At being composed in her heart and mind. beautiful woman she had become, she the age of 40, it might have seemed too There was an untold story in the music had sorrowfully watched him grow into late to ask the inevitable question, “who that she could feel but whose meaning the old exhausted man he now was. She am I?” But the relief of being able to willshe couldn’t quite reveal. would sneak into his room at night and ingly re-live life with every new mornFor many years, a mundane life was count every breath he took, then stare ing had opened the door of possibilities imposed upon her rebellious soul, tam- into infinity to remember how life never once more. ing it into something obscure and per- gives back what it takes. The sacredly promised wind of change plexing. Alone in a small apartment in a Years later, she was facing life alone; had squalled into her dull life. At the village outside the city, a small bedroom the ultimate destiny of man, it appears. age of 40, she had decided to blossom overlooking a window and garden on She was an eminent teacher at the same through a long awaited twist of fate. She a quiet street, she lived in infuriating university where she once graduated. was going to be a Nurse. She was revived solitude filled with nothing but memo- But success may have nothing to do with by a simple dream added to her stagnant ries. Perhaps men are destined to be happiness and achievement may be con- life like a magical spark. And after the indeprived of their ambitions the moment strained by the features of the time we evitable passing of time, she stood there life becomes one of frivolous aims and live in. Van Gogh, the painter, was never in front of the small nursing home, waitselfish causes without real value? But famous when he was alive and died hav- ing for life to blossom once more in her then, there were days when Isabella felt ing sold a single painting. Nietzsche, the heart. The glow of humble achievement nothing; hollow emptiness would perme- wise and sincerely redeemed philoso- had lit up her eyes. She remembered her ate her soul so profoundly as though pher who praised all values in life, never father, her childhood, her successes and she was experiencing death with a sub- got to experience many of the joys of failures. And though the wind of change conscious mind. Unfortunately, to man's life. And Jane Austen, the romantic au- had struck her life mercilessly on many despair, even nothingness is an unlivable thor, never enjoyed the loving embrace occasions; for Isabella, it was now the ulpain. or tender touch of a lover. timate gift. The gift of change. Almost 20 years ago, Isabella was a And as such, Isabella who gave highly new graduate from one of the most pres- praised lectures on social behavior had tigious universities. She was beautiful been living a life of social disengagement. and smart and, above all, self-confident. What good does it do to mourn, Isabella She walked around on her graduation always asked herself? Why is the world ceremony, her long brown hair braided so intangibly constant, yet comprised of with flowers below her graduation cap. infinite dynamicity? Was she destined to Her eyes glowed with the pride of her be miserable or was she perceiving the Yasmine Yousri Said, success, and her lips ceased not grin- world the wrong way? For as long as Isa- MSc student, ning. In the graduation hall, an old man bella had begun to create her own per- Erasmus Mundus Neurasmus
2014 International Graduate Program Medical Neurosciences
CNSNewsletter September 2014
Topic
www.medical-neurosciences.de
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News in Brief & WhazzUp?
Senior Students Show Off Master Theses On Friday, October 10th, the senior students will present their master’s theses as part of their graduation ceremony. From 3 PM on, the celebrations begin with presentations of the master projects, followed by a reception and welcome party for the new students. This bitter sweet event symbolically hands over the torch to the next generation of students. September 3-7
Berlin Music Week (http://www.berlin-music-week.de/en/festival/)
4-14
Days of Jewish Culture (http://bit.ly/VVsQ7q)
4-22
Music Festival Berlin (http://bit.ly/U1ixNz)
10-20
International Literature Festival Berlin (http://bit.ly/1mvybvl)
12-14
Entheo-Science Congress 2014 (http://entheo-science.de/en)
14
Heritage Day/Tag des Offenen Denkmals (http://tag-des-offenen-denkmals.de/)
16-21
Berlin Art Week (http://www.berlinartweek.de/en.html)
17-20
25th European Students‘ Conference (http://www.esc-berlin.com/)
18-20
SFB665 Symposium 2014: Developmental Disturbances in the Nervous System (www.sfb665.de/Symposium2014)
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28. Treffpunkt Medizintechnik “Biologisierte Medizintechnik” (http://www.healthcapital.de/tp-med)
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Berlin Marathon (http://www.bmw-berlin-marathon.com/en/)
10-19
Festival of Lights (http://festival-of-lights.de/en/)
18-21
27th Congress of the European College of Neuropsychopharmacology (ECNP2013) (http://www.ecnp.eu/)
19-22
Annual Meeting of the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) (http://www.dgkn-kongress.de)
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World Stroke Day
30
Jazz Festival Berlin (http://bit.ly/1gcxsNE)
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International Symposium Immunology of mucosa (http://www.sfb650.charite. de/aktuelles/registration_symposium_ immunology_of_mucosa)
November
26-29
3rd Neurasmus Meeting Rocks Berlin’s Office From July 10-16th, the 3rd Neurasmus meeting rocked our Berlin office kicking off with 5-minute presentations of theses and posters. Other than the board meetings to discuss formalities, scientific workshops which included one on scientific writing and thought-provoking lectures were the major scientific highlights and were well received. Tours of the Cold War in Berlin and to Potsdam’s Sanssouci as well as dinners at distinct places combined history, science, and culture in and around Berlin making it an eventful six days for the students. From Berlin with Love: we greet all Neurasmus students and partner universities in Amsterdam, Bordeaux, Coimbra, Goettingen, and Laval! MedNeuro to Welcome 26 New Master Students The office will be busy, without a doubt with the arrival of 26 new students. Fifteen MedNeuros, five 1st-year and six 2nd-year Neurasmus students. The senior students will keep them away from known pitfalls, provide tips and hints, and show them our campus and Berlin. Meanwhile, we will hassle them with administrative issues and regulations of the program. Our ‘pay back’ will be city tours, casual get-togethers, and dinners. We look forward to meeting all the new students from around the world! MedNeuro PhD Family Gets Bigger The Admission Committee meeting on June 24 admitted six new PhD students to our program. A very warm welcome to: Claudia Bentz (Eickholt), Magdalena Jochner (Harms), Priscilla Koduah (Meisel), Lauren Mamer (Rosenmund), Daniele Mattei (Kettenmann), and Ira Strübing (Basta). Claudia and Magdalena are successful applicants of last year’s NeuroCure PhD fellowships. Lauren and Priscilla graduated from our Master’s program in 2011 and 2013, respectively. Lauren is currently taking a leave of absence from medical school in the US to work on her PhD project. Imprint
October
11-16
CNSNewsletter September 2014
International Short Film Festival Berlin (http://bit.ly/1qS1JXp) German Association of Psychiatry, Psychotherapy and Psychosomatics (DGPPN) annual congress (http://www.dgppn.de/kongress.html)
2014 International Graduate Program Medical Neurosciences
Charité NeuroScience (CNS) Newsletter Correspondence Charité – Universitätsmedizin Berlin International Graduate Program Medical Neurosciences, Charitéplatz 1, 10117 Berlin
[email protected], t: +49 30 2093-4585 f: +49 30 2093-4590 Contact
[email protected] Editor-in-Chief Marietta Zille Editors Ahmed Khalil Apoorva Rajiv Madipakkam Constance Holman Jennifer Flynn Luke Tudge Design Viktoria Stoiser Cover Betty Jurek