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DNA Modifications in the Brain

DNA Modifications in the Brain Book
Author : Timothy W. Bredy
Publisher : Academic Press
Release : 2017-01-05
ISBN : 9780128015964
Language : En, Es, Fr & De

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Book Description :

DNA Modifications in the Brain: Neuroepigenetic Regulation of Gene Expression begins with an historical overview of the early discoveries surrounding DNA methylation in the mammalian brain and then explores the evidence supporting a role for this epigenetic mechanism in controlling gene expression programs across the lifespan in both normal and diseased states. Chapters describe new directions and technological advances, and provide an overview of what the future holds for this exciting new field. This book is ideal for medical, graduate and advanced undergraduate students, but is also a great resource for researchers who need a broad introduction to the dynamic nature of DNA that sheds light on evolving concepts of gene-environment interaction and their effects on adaptation and neuropsychiatric disease. Provides a comprehensive overview of the many facets of DNA modifications Discusses the impact of this dynamic epigenetic mechanism across brain development and lifespan at behavioral, cognitive, molecular and genetic levels Contains contributions by influential leaders in the field Edited by a Neuroscientist to further promote synthesis between epigenetics, neuroscience, and clinical relevance

Epigenetics Brain and Behavior

Epigenetics  Brain and Behavior Book
Author : Paolo Sassone Corsi,Yves Christen
Publisher : Springer Science & Business Media
Release : 2012-10-19
ISBN : 3642279139
Language : En, Es, Fr & De

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Book Description :

Recent years have seen spectacular advances in the filed of epigenetics. These have attracted the interest of researchers in many fields and evidence connecting epigentic regulation to brain functions has been accumulationg. Neurons daily convert a variety of external stimuli into rapid or long-lasting changes in gene expression. A variety of studies have centered on the molcular mechanisms implicated in epigentic control and how these may operte in concert. It will be critical to unravel how specifity is achieved. The focus of this volume is on critical epigenetic regulation and chromatin remodeling events that occur in the nervous system and on the presumed mechanisms that operate within neurons to translate them into long-lasting neuronal responses.

The Epigenetics of Suicide

The Epigenetics of Suicide Book
Author : Benoit Labonté
Publisher : Unknown
Release : 2013
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

"Suicide is a problem resulting from the interaction between several factors. Among these factors, early-life adversity, characterized by child sexual and physical abuse as well as parental neglect, is one of the strongest risk factors for depression and suicidal behaviors. While it is clear that child abuse increases the risk for depression and suicide, the mechanisms mediating these effects are still unknown. Recent evidences suggest that epigenetic mechanisms may be involved in mediating the effects of early-life adversity on behavior. Early-life stress in animals has been shown to alter DNA methylation in genes regulatory regions what, in turn, has been associated with changes in gene expression and behavioral modifications. Importantly, similar changes have been reported in several genes in the human brain. However, although epigenetic modifications have been found in several genes, the extent of epigenetic changes induced by early-life adversity is still unknown and their impacts on increasing suicide risk are unclear. This thesis aims at expanding our understanding of suicide by investigating one potential mechanism by which early-life adversity may increase vulnerability to mood disorders and suicide, namely epigenetic regulation of gene expression. We first expanded our characterization of DNA methylation alterations induced by early and adult-life stress in the regulatory regions of the glucocorticoid receptor gene which is one of the most consistent alterations associated with stress, depression and suicidal behaviors. We then opted for a genome-wide characterization of DNA methylation alterations found in the brains of suicide completers with and without a history of child abuse using microarray analyses focusing on gene promoters throughout the genome. Our findings revealed several DNA methylation alterations in genes with known roles on behavioral regulation and identified several new genes and networks which may be specifically altered by early-life adversity. We also characterized the functional impact of these alterations on gene expression and promoter transcriptional activity. Overall, this work identifies and characterizes the molecular mechanisms by which environment induces behavioral changes conferring vulnerability toward mood disorders and suicidal behaviors. " --

DNA Modifications in the Brain

DNA Modifications in the Brain Book
Author : Timothy W Bredy
Publisher : Academic Press
Release : 2016-12-23
ISBN : 0128017813
Language : En, Es, Fr & De

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Book Description :

DNA Modifications in the Brain: Neuroepigenetic Regulation of Gene Expression begins with an historical overview of the early discoveries surrounding DNA methylation in the mammalian brain and then explores the evidence supporting a role for this epigenetic mechanism in controlling gene expression programs across the lifespan in both normal and diseased states. Chapters describe new directions and technological advances, and provide an overview of what the future holds for this exciting new field. This book is ideal for medical, graduate and advanced undergraduate students, but is also a great resource for researchers who need a broad introduction to the dynamic nature of DNA that sheds light on evolving concepts of gene-environment interaction and their effects on adaptation and neuropsychiatric disease. Provides a comprehensive overview of the many facets of DNA modifications Discusses the impact of this dynamic epigenetic mechanism across brain development and lifespan at behavioral, cognitive, molecular and genetic levels Contains contributions by influential leaders in the field Edited by a Neuroscientist to further promote synthesis between epigenetics, neuroscience, and clinical relevance

The Effects of Sodium Butyrate NaB and Maltreatment Early in Postnatal Development on DNA Methylation in the Hippocampus and Amygdala of Adult Male Rats

The Effects of Sodium Butyrate  NaB  and Maltreatment Early in Postnatal Development on DNA Methylation in the Hippocampus and Amygdala of Adult Male Rats Book
Author : Isabella Archer
Publisher : Unknown
Release : 2019
ISBN : 9781085636933
Language : En, Es, Fr & De

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Book Description :

Early life stress, especially childhood maltreatment, increases the risk for cognitive dysfunction and mental problems later in life. Studies have sought to identify how these phenotypes come about by examining structural and functional changes in various brain regions. Recent work has also focused on identifying whether changes in DNA methylation, an epigenetic modification that helps regulate gene transcription important for the structural and functional capacity of the brain, is also responsible for phenotypic outcomes. Using a rat model, we investigated whether maltreatment leaves long-term epigenetic modifications on DNA associated with the brain-derived neurotrophic factor (bdnf) gene in the adult amygdala and hippocampus and whether administering an epigenome modifying drug (sodium butyrate, NaB) at the time of maltreatment prevents these epigenetic modifications. We focused on the bdnf gene as it is critical for structural and functional capacity of the brain and known to be sensitive to early life stress. During first post-natal week, infant male rats were either administered NaB or a vehicle solution and exposed to either maltreatment or nurturing maternal care. We then assessed DNA methylation after pups reached adulthood. We replicate observations we made in a previous report that exposure to maltreatment alters bdnf DNA methylation in the amygdala and hippocampus. We also find concurrent administration of NaB with maltreatment capable of changing patterns of methylation. These results provide further empirical support that DNA methylation modifications are biological consequences of experiences within the caregiving environment and highlight the ability to potentially intervene and change epigenetic trajectories.

Brain Behavior and Epigenetics

Brain  Behavior and Epigenetics Book
Author : Arturas Petronis,Jonathan Mill
Publisher : Springer Science & Business Media
Release : 2011-05-19
ISBN : 9783642174261
Language : En, Es, Fr & De

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Book Description :

Biomedical research in the first decade of the 21st century has been marked by a rapidly growing interest in epigenetics. The reasons for this are numerous, but primarily it stems from the mounting realization that research programs focused solely on DNA sequence variation, despite their breadth and depth, are unlikely to address all fundamental aspects of human biology. Some questions are evident even to non-biologists. How does a single zygote develop into a complex multicellular organism composed of dozens of different tissues and hundreds of cell types, all genetically identical but performing very different functions? Why do monozygotic twins, despite their stunning external similarities, often exhibit significant differences in personality and predisposition to disease? If environmental factors are solely the cause of such variation, why are similar differences also observed between genetically identical animals housed in a uniform environment? Over the last couple of decades, epigenetics has undergone a significant metamorphosis from an abstract developmental theory to a very dynamic and rapidly developing branch of molecular biology. This volume represents a compilation of our current understanding about the key aspects of epigenetic processes in the brain and their role in behavior. The chapters in this book bring together some of the leading researchers in the field of behavioral epigenetics. They explore many of the epigenetic processes which operate or may be operating to mediate neurobiological functions in the brain and describe how perturbations to these systems may play a key role in mediating behavior and the origin of brain diseases.

Patho Epigenetics of Disease

Patho Epigenetics of Disease Book
Author : Janos Minarovits,Hans Helmut Niller
Publisher : Springer Science & Business Media
Release : 2012-06-14
ISBN : 1461433452
Language : En, Es, Fr & De

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Book Description :

In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences. Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to “remember” their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of human diseases.

The DNA RNA and Histone Methylomes

The DNA  RNA  and Histone Methylomes Book
Author : Stefan Jurga,Jan Barciszewski
Publisher : Springer Nature
Release : 2019-08-28
ISBN : 3030147924
Language : En, Es, Fr & De

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Book Description :

This book reviews the chemical, regulatory, and physiological mechanisms of protein arginine and lysine methyltransferases, as well as nucleic acid methylations and methylating enzymes. Protein and nucleic acid methylation play key and diverse roles in cellular signalling and regulating macromolecular cell functions. Protein arginine and lysine methyltransferases are the predominant enzymes that catalyse S-adenosylmethionine (SAM)-dependent methylation of protein substrates. These enzymes catalyse a nucleophilic substitution of a methyl group to an arginine or lysine side chain nitrogen (N) atom. Cells also have additional protein methyltransferases, which target other amino acids in peptidyl side chains or N-termini and C-termini, such as glutamate, glutamine, and histidine. All these protein methyltransferases use a similar mechanism. In contrast, nucleic acids (DNA and RNA) are substrates for methylating enzymes, which employ various chemical mechanisms to methylate nucleosides at nitrogen (N), oxygen (O), and carbon (C) atoms. This book illustrates how, thanks to there ability to expand their repertoire of functions to the modified substrates, protein and nucleic acid methylation processes play a key role in cells.

Epigenetics and Neuroplasticity Evidence and Debate

Epigenetics and Neuroplasticity   Evidence and Debate Book
Author : Schahram Akbarian,Farah Lubin
Publisher : Academic Press
Release : 2014-11-12
ISBN : 9780128009772
Language : En, Es, Fr & De

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Book Description :

The 'epi-(Greek for 'over', 'above')genome', with its rich cache of highly regulated, structural modifications-including DNA methylation, histone modifications and histone variants-defines the moldings and three-dimensional structures of the genomic material inside the cell nucleus and serves, literally, as a molecular bridge linking the environment to the genetic materials in our brain cells. Due to technological and scientific advances in the field, the field of neuroepigenetics is currently one of the hottest topics in the basic and clinical neurosciences. The volume captures some of this vibrant and exciting new research, and conveys to the reader an up-to-date discussion on the role of epigenetics across the lifespan of the human brain in health and disease. Topics cover the entire lifespan of the brain, from transgenerational epigenetics to neurodevelopmental disease to disorders of the aging brain. All chapters are written with dual intent, to provide the reader with a timely update on the field, and a discussion of provocative or controversial findings in the field with the potential of great impact for future developments in the field.

Stem Cell Epigenetics

Stem Cell Epigenetics Book
Author : Anonim
Publisher : Academic Press
Release : 2020-08-13
ISBN : 0128140852
Language : En, Es, Fr & De

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Book Description :

Stem Cell Epigenetics, Volume 16, examines how epigenetics are involved in stem cell differentiation, how a stem cell rapidly transitions into a molecularly distinct cell type, and how this process may be reversed or managed via epigenetic reprogramming. Topics discussed include chromatin in pluripotency, epigenetic regulation of reprogramming, stem cells and DNA methylation, histone modifications in stem cells and differentiation, higher-order chromatin conformation in pluripotent cells, epigenetics and disease modeling, organoids from pluripotent cells, transcriptional regulation in stem cells and differentiation, non-coding RNAs in pluripotency and early differentiation, and diseases caused by epigenetic alterations in stem cells. Additionally, the potential implementation of stem cell epigenetics in drug discovery, regenerative medicine, and disease treatment is discussed in detail, helping researchers and physicians bring this exciting and fast evolving field to the clinic. Provides genetic researchers, students and physicians with evidence indicating the epigenetic mechanisms involved in stem cell differentiation Highlights the specific characteristics of the epigenetic modifications and misregulations that may result in disease pathogenesis Examines the potential application of stem cell epigenetics towards developing therapeutic interventions for disease and advancing regenerative medicine Features chapter contributions by leading international experts

Sex and the Developing Brain

Sex and the Developing Brain Book
Author : Margaret M. McCarthy
Publisher : Biota Publishing
Release : 2017-08-31
ISBN : 1615047298
Language : En, Es, Fr & De

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Book Description :

The brains of males and females, men and women, are different, that is a fact. What is debated is how different and how important are those differences. Sex differences in the brain are determined by genetics, hormones, and experience, which in humans includes culture, society, and parental and peer expectations. The importance of nonbiological variables to sex differences in humans is paramount, making it difficult if not impossible to parse out those contributions that are truly biological. The study of animals provides us the opportunity to understand the magnitude and scope of biologically based sex differences in the brain, and understanding the cellular mechanisms provides us insight into novel sources of brain plasticity. Many sex differences are established during a developmental sensitive window by differences in the hormonal milieu of males versus females. The neonatal testis produces large amounts of testosterone which gains access to the brain and is further metabolized into active androgens and estrogens which modify brain development. Major parameters that are influenced by hormones include neurogenesis, cell death, neurochemical phenotype, axonal and dendritic growth, and synaptogenesis. Variance in these parameters results in sex differences in the size of particular brain regions, the projections between brain regions, and the number and type of synapses within particular brain regions. The cellular mechanisms are both region and endpoint specific and invoke many surprising systems such as prostaglandins, endocannabinoids, and cell death proteins. Epigenetic modifications to the genome both establish and maintain sex differences in the brain and behavior. By understanding when, why, and how sex differences in the brain are established, we may also learn the source of strong gender biases in the relative risk and severity of numerous neurological diseases and disorders of mental health. Boys are much more likely to be diagnosed with autism spectrum or attention and hyperactivity disorders, as well as speech and language deficits, compared to girls. By contrast, women are more likely to suffer from affective disorders, such as depression, anxiety, compulsion, and eating disorders and more likely to experience autoimmune and neurodegenerative disorders. Schizophrenia with an early onset is more common in males but a late-onset version is markedly more frequent in females. Male biased disorders have origins in development while female biased disorders are almost exclusively post-puberty. This remarkable shift in disease risk demands our attention. Novel insights into the biological origins of disease are also gained by comparing and contrasting the same processes in different sexes.

DNA Methylation and Cocaine Dependence in the Human Striatum

DNA Methylation and Cocaine Dependence in the Human Striatum Book
Author : Kathryn Vaillancourt
Publisher : Unknown
Release : 2021
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

"Cocaine use disorder (CUD) is a chronic relapsing brain disease that involves cycles of intoxication, withdrawal, and preoccupation. CUD impacts 1-2% of the population worldwide, and although there are multiple lines of evidence that report lasting changes in neurobiology, the mechanisms that accompany the development and maintenance of the disorder are not well understood. Work in animal models suggests that epigenetic mechanisms, including histone post translational modifications and DNA methylation, might be important regulators of cocaine-related changes to cell functioning, but to date, little is known about the relationship between cocaine dependence and epigenetics in humans.This thesis presents the first methylome-wide investigations in human post-mortem brain, using multiple cohorts of banked samples, from two addiction-relevant brain regions; the nucleus accumbens which is highly implicated in the motivational effects of drug use, and the caudate nucleus which is involved in compulsive drug-seeking behaviors. We use reduced representation bisulfite sequencing (RRBS) and identified and characterized over 100 differentially methylated regions (DMRs) in both brain areas. We also report on two novel intragenic regulatory elements which are differentially methylated in the neurons of cocaine dependent subjects — a CTCF binding element within the Iroquois homeobox 2 gene (IRX2) which regulates local three-dimensional chromatin structure, and an EGR1 binding element within the tyrosine hydroxylase gene (TH) which acts as a methylation-sensitive enhancer of gene expression. This work represents an important first step towards understanding the role of DNA methylation in the pathophysiology of CUD in humans and provides numerous avenues for further investigation"--

Epigenetic pathways in PTSD how traumatic experiences leave their signature on the genome

Epigenetic pathways in PTSD  how traumatic experiences leave their signature on the genome Book
Author : Tania L Roth,David M Diamond,Karestan C Koenen
Publisher : Frontiers Media SA
Release : 2015-04-14
ISBN : 2889194582
Language : En, Es, Fr & De

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Book Description :

This research topic focuses on epigenetic components of PTSD. Epigenetic mechanisms are a class of molecular mechanisms by which environmental influences, including stress, can interact with the genome to have long-term consequences for brain plasticity and behavior. Articles herein include empirical reports and reviews that link stress and trauma with epigenetic alterations in humans and animal models of early- or later-life stress. Themes present throughout the collection include: DNA methylation is a useful biomarker of stress and treatment outcome in humans; epigenetic programming of stress-sensitive physiological systems early in development confers an enhanced risk on disease development upon re-exposure to trauma or stress; and, long-lived fear memories are associated with epigenetic alterations in fear memory and extinction brain circuitry.

Neuroepigenomics in Aging and Disease

Neuroepigenomics in Aging and Disease Book
Author : Raul Delgado-Morales
Publisher : Springer
Release : 2017-05-18
ISBN : 3319538896
Language : En, Es, Fr & De

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Book Description :

Epigenetic mechanisms (DNA modifications, histone alterations and non-coding RNAs) are crucial for transcriptional regulation and alterations of the “physiological epigenome” are increasingly associated with human diseases. During the last decade the emerging field of neuroepigenomics have started to impact tremendously in areas such learning and memory, addiction or neurodegeneration. This expert volume covers the role of epigenetic molecular mechanism in regulation of central nervous system’s function, one of the most exciting areas of contemporary molecular neuroscience. The book describes the current knowledge on the epigenetic basis of human disease covering the complete lifespan: from neurodevelopment/childhood (Rett Syndrome, Rubinstein-Taybi, autism), adolescence (eating disorders, drug addiction, anxiety), adulthood (depression, schizophrenia, amyotrophic lateral sclerosis, Huntington’s disease) and elderly (Alzheimer’s disease, Parkinson’s disease). The book also covers the three major players on neuroepigenomic mechanisms: histones alterations, DNA modifications and non-coding RNAs, their roles at the molecular and cellular level and the impact of their alterations on neuronal function and behavior. Finally, a special chapter on state-of-the-art technologies helps the reader not only to understand epigenetic driven changes in human cognition and diseases but also the methodology that will help to generate paradigm shifts on our understanding of brain function and the role of the neuroepigenome in human diseases.

Genetics and Epigenetics of Fetal Alcohol Spectrum Disorders

Genetics and Epigenetics of Fetal Alcohol Spectrum Disorders Book
Author : Feng C. Zhou,Stephen Mason
Publisher : Frontiers Media SA
Release : 2015-08-06
ISBN : 2889195732
Language : En, Es, Fr & De

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Book Description :

Women drinking during pregnancy can result in Fetal Alcohol Spectrum Disorder (FASD), which may feature variable neurodevelopmental deficits, facial dysmorphology, growth retardation, and learning disabilities. Research suggests the human brain is precisely formed through an intrinsic, genetic-cellular expression that is carefully orchestrated by an epigenetic program. This program can be influenced by environmental inputs such as alcohol. Current research suggests the genetic and epigenetic elements of FASD are heavily intertwined and highly dependent on one another. As such, now is the time for investigators to combine genetic, genomic and epigenetic components of alcohol research into a centralized, accessible platform for discussion. Genetic analyses inform gene sets which may be vulnerable to alcohol exposure during early neurulation. Prenatal alcohol exposure indeed alters expression of gene subsets, including genes involved in neural specification, hematopoiesis, methylation, chromatin remodeling, histone variants, eye and heart development. Recently, quantitative genomic mapping has revealed loci (QTLs) that mediate alcohol-induced phenotypes identified between two alcohol-drinking mouse strains. One question to consider is (besides the role of dose and stage of alcohol exposure) why only 5% of drinking women deliver newborns diagnosed with FAS (Fetal Alcohol Syndrome)? Studies are ongoing to answer this question by characterizing genome-wide expression, allele-specific expression (ASE), gene polymorphisms (SNPs) and maternal genetic factors that influence alcohol vulnerability. Alcohol exposure during pregnancy, which can lead to FASD, has been used as a model to resolve the epigenetic pathway between environment and phenotype. Epigenetic mechanisms modify genetic outputs through alteration of 3D chromatin structure and accessibility of transcriptional machinery. Several laboratories have reported altered epigenetics, including DNA methylation and histone modification, in multiple models of FASD. During development DNA methylation is dynamic yet orchestrated in a precise spatiotemporal manner during neurulation and coincidental with neural differentiation. Alcohol can directly influence epigenetics through alterations of the methionine pathway and subsequent DNA or histone methylation/acetylation. Alcohol also alters noncoding RNA including miRNA and transposable elements (TEs). Evidence suggests that miRNA expression may mediate ethanol teratology, and TEs may be affected by alcohol through the alteration of DNA methylation at its regulatory region. In this manner, the epigenetic and genetic components of FASD are revealing themselves to be mechanistically intertwined. Can alcohol-induced epigenomic alterations be passed across generations? Early epidemiological studies have revealed infants with FASD-like features in the absence of maternal alcohol, where the fathers were alcoholics. Novel mechanisms for alcohol-induced phenotypes include altered sperm DNA methylation, hypomethylated paternal allele and heritable epimutations. These studies predict the heritability of alcohol-induced epigenetic abnormalities and gene functionality across generations. We opened a forum to researchers and investigators the field of FASD to discuss their insights, hypotheses, fresh data, past research, and future research themes embedded in this rising field of the genetics and epigenetics of FASD. This eBook is a product of the collective sharing and debate among researchers who have contributed or reviewed each subject.

Genetics and Epigenetics of Psychiatric Diseases 2nd Edition

Genetics and Epigenetics of Psychiatric Diseases  2nd Edition Book
Author : Cunyou Zhao,Weihua Yue,Zhexing Wen
Publisher : Frontiers Media SA
Release : 2020-10-09
ISBN : 2889660257
Language : En, Es, Fr & De

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Book Description :

Psychiatric diseases have a highly complex etiology, aggregating in families but not segregating in a traditional Mendelian manner. Recent approaches to understanding the causes of psychiatric disease have focused on describing the genetic contribution to major psychiatric illnesses; the use of large-scale genome-wide association studies (GWAS) and exome sequencing has enabled a systematic exploration of genetic risk factors and identified over 100 independent genomic loci significantly associated with psychiatric diseases; however, there remains uncertainty about the causal genes involved in disease pathogenesis, and how their function is regulated. Since many GWAS variants reside in non-coding regions, the disease-associated common variants might be enriched in regulatory domains, including enhancers and regions of active chromatin state. These lead us to focus on the possible role of non-sequence-based genomic variation in health and disease. Of particular interest are epigenetic modifications that regulate gene expression through modifications to DNA, RNA, histone proteins, and chromatin. The availability of high-throughput profiling methods for quantifiying epigenomic modifications in large numbers of samples has enabled us to perform epigenome-wide association studies (EWAS) aimed at screening methylomic variations associated with environmental exposure and disease. Thus systematic integration of genetic, epigenetic and epidemiological approaches will contribute to improving our understanding of the molecular mechanisms underlying disease phenotypes.

Search for DNA Methylation Differences in Major Psychosis

Search for DNA Methylation Differences in Major Psychosis Book
Author : Simin Yazdanpanah
Publisher : Unknown
Release : 2007
ISBN : 9780494403709
Language : En, Es, Fr & De

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Book Description :

Epigenetic modifications comprise a code of information on DNA, independent of the DNA sequence content that may contribute to phenotypic differences. Epigenetic dysregulation of gene transcription can play a role in the etiology of human disease. Epigenetic dysregulation is consistent with various non-Mendelian features of major psychosis. In this study I demonstrate the existence of DNA methylation differences in the post mortem brain tissues of schizophrenia and bipolar disorder patients compared to controls. The experimental strategy included verification of microarray data at specific loci by site specific DNA methylation analysis using pyrosequencing methodology. The results of this study prove that epigenetic changes are associated with major psychosis. In addition, a novel whole genome amplification technique was developed to amplify the bisulfite modified DNA that represents a significant improvement in the large scale high throughput DNA methylation analysis of multiple loci.

The Effects of Chromosomal Composition and Hormonal Influences on Shaping Sex Differences in the Developing Mammalian Brain

The Effects of Chromosomal Composition and Hormonal Influences on Shaping Sex Differences in the Developing Mammalian Brain Book
Author : Matthew Scott Bramble
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic brain development, we identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. RNA-sequencing identified 103 transcripts that were differentially expressed between XX and XY eNSCs at baseline (FDR=0.10). Treatment with testosterone-propionate (TP) reveals sex-specific gene expression changes, causing 2854 and 792 transcripts to become differentially expressed on XX and XY genetic backgrounds respectively. These findings indicate that testosterone exposure on XX cells have a more robust effect with regards to altering gene expression. It was also found that by exposing XX eNSCs to TP, 42% (43/103) of the original 103 basal sex differences that existed became masculinized and shifted towards a XY typical gene expression pattern. We also determined that 25% (26/103) of basal sex differences were actually feminized in an XY background post-TP. These alteration in gene expression post-TP exposure were determine to require functional androgen receptor (AR), as AR knockout (ARKO) eNSCs did not show differential expression of select genes in the presence of TP. Within the TP responsive transcripts, there was enrichment for genes which function as epigenetic regulators that affect both histone modifications and DNA methylation patterning, specifically Tet proteins, known to function as a DNA demethylases. We observed that TP caused a global decrease in 5-methylcytosine abundance in both sexes, a transmissible effect that was maintained in cellular progeny. Like gene expression, alteration in DNA methylation function downstream of AR activation, with ARKO lines showing no significant androgen induced DNA de-methylation. Additionally, we determined that TP was associated with residue-specific alterations in acetylation of histone tails. Collectively, these findings highlight an unknown component of androgen action on cells within the developmental CNS, and contribute to a novel mechanism of action by which early hormonal organization is initiated and maintained.

The Neurobiology of Brain and Behavioral Development

The Neurobiology of Brain and Behavioral Development Book
Author : Robbin Gibb,Bryan Kolb
Publisher : Academic Press
Release : 2017-11-02
ISBN : 012804084X
Language : En, Es, Fr & De

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Book Description :

The Neurobiology of Brain and Behavioral Development provides an overview of the process of brain development, including recent discoveries on how the brain develops. This book collates and integrates these findings, weaving the latest information with core information on the neurobiology of brain development. It focuses on cortical development, but also features discussions on how the other parts of the brain wire into the developing cerebral cortex. A systems approach is used to describe the anatomical underpinnings of behavioral development, connecting anatomical and molecular features of brain development with behavioral development. The disruptors of typical brain development are discussed in appropriate sections, as is the science of epigenetics that presents a novel and instructive approach on how experiences, both individual and intergenerational, can alter features of brain development. What distinguishes this book from others in the field is its focus on both molecular mechanisms and behavioral outcomes. This body of knowledge contributes to our understanding of the fundamentals of brain plasticity and metaplasticity, both of which are also showcased in this book. Provides an up-to-date overview of the process of brain development that is suitable for use as a university textbook at an early graduate or senior undergraduate level Breadth from molecular level (Chapters 5-7) to the behavioral/cognitive level (Chapters 8-12), beginning with Chapters 1-4 providing a historical context of the ideas Integrates the neurobiology of brain development and behavior, promoting the idea that animal models inform human development Presents an emphasis on the role of epigenetics and brain plasticity in brain development and behavior

Hormones Brain and Behavior

Hormones  Brain and Behavior Book
Author : Anonim
Publisher : Academic Press
Release : 2016-11-09
ISBN : 0128036087
Language : En, Es, Fr & De

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Book Description :

Hormones, Brain and Behavior, Third Edition offers a state-of-the-art overview of hormonally-mediated behaviors, including an extensive discussion of the effects of hormones on insects, fish, amphibians, birds, rodents, and humans. Entries have been carefully designed to provide a valuable source of information for students and researchers in neuroendocrinology and those working in related areas, such as biology, psychology, psychiatry, and neurology. This third edition has been substantially restructured to include both foundational information and recent developments in the field. Continuing the emphasis on interdisciplinary research and practical applications, the book includes articles aligned in five main subject sections, with new chapters included on genetic and genomic techniques and clinical investigations. This reference provides unique treatment of all major vertebrate and invertebrate model systems with excellent opportunities for relating behavior to molecular genetics. The topics cover an unusual breadth (from molecules to ecophysiology), ranging from basic science to clinical research, making this reference of interest to a broad range of scientists in a variety of fields. Comprehensive and updated coverage of a rapidly growing field of research Unique treatment of all major vertebrate and invertebrate model systems with excellent opportunities for relating behavior to molecular genetics Covers an unusual breadth of topics and subject fields, ranging from molecules to ecophysiology, and from basic science to clinical research Ideal resource for interdisciplinary learning and understanding in the fields of hormones and behavior