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Epigenetic Regulation in the Nervous System - 1st Edition - ISBN: 9780123914941, 9780123944054

Epigenetic Regulation in the Nervous System

1st Edition

Basic Mechanisms and Clinical Impact

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Editors: J. David Sweatt Michael J. Meaney Eric Nestler Schahram Akbarian
Hardcover ISBN: 9780123914941
eBook ISBN: 9780123944054
Imprint: Academic Press
Published Date: 8th February 2013
Page Count: 374
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Epigenetic Regulation in the Nervous System addresses current understanding of the roles of epigenetic processes at the molecular/cellular level, their impact on neural development and behavior, and the potential roles of these mechanisms in neurological and psychiatric disorders. This award-winning volume spans molecular epigenetics, development, cellular physiology and biochemistry, synaptic and neural plasticity, and behavioral models, and is unique in covering epigenetically based disorders of the central nervous system.

Behavioral epigenetics is the study of how environmental factors alter behavior, addressing the fundamental mechanisms that shape development and individual vulnerability/resilience to adverse behavioral outcomes. By understanding the molecular mechanisms involved in epigenetic modulation, researchers may be able to develop targeted therapies for those individuals in whom it malfunctions.

Edited by the most highly regarded leaders in the field, this book offers a comprehensive review of behavioral epigenetics and a balanced treatment of the strengths and weaknesses in experimentation in this area. Covering background material as well as topics of current interest, it serves both as a cutting-edge resource and a foundational reference. The book will benefit neuroscience researchers and graduate students with an interest in the links between gene regulation and behavior, as will clinicians dealing with disorders such as addiction, depression, and schizophrenia.

Key Features

  • BMA Medical Book Awards 2014 - Highly Commended,  Neurology, British Medical Association
  • BMA Medical Book Awards 2014 - First Prize, Neurology, British Medical Association
  • 2013 PROSE Award winner for Best in Reference Works and Best Single Volume Reference in Science from the Association of American Publishers
  • Presents a unified view of epigenetic mechanisms from behavior to genes and everything in between
  • Discusses clinically relevant disorders in the context of epigenetics research, making the volume appealing to clinicians as well as basic scientists
  • Provides numerous practical examples for the new investigator to facilitate implementation of research in neuroepigenetics


Researchers and advanced students in molecular/cellular, developmental and behavioral neuroscience; clinical neuroscientists; research psychiatrists and psychologists

Table of Contents


List of Contributors

Chapter 1. An Overview of the Molecular Basis of Epigenetics


DNA Modifications

Histone Modifications

Non-Coding RNAs

Non-Genic DNA

Prion-Based Epigenetic Inheritance

Epigenome Organization and Higher Order Chromatin Structures

Roles for Epigenetic Mechanisms in the Nervous System

Epigenetic Mechanisms in Nervous System Development

Neurogenesis in the Adult CNS

Circadian Rhythms

Persisting Effects of Life Experience: Nurturing and Transgenerational Effects

Epigenetic Mechanisms and Cellular Information Storage

Human Cognition and Cognitive Disorders

Summary – Active Regulation of Epigenetic Marks in the Nervous System


Chapter 2. Histone Modifications in the Nervous System and Neuropsychiatric Disorders


The Histone Code: Complex and Combinatorial

Other Epigenetic Mechanisms


The Histone Code in Learning, Memory and Synaptic Plasticity

The Histone Code in Neurological and Neuropsychiatric Disorders

Neurodevelopmental Disorders and Intellectual Disability

Mood Disorders




Chapter 3. Active DNA Demethylation and 5-Hydroxymethylcytosine


Regulation of Neuronal Gene Expression by Active DNA Demethylation

Active DNA Demethylation Mediated by DNA Repair

TET Proteins and an Oxidative Demethylation Pathway

Functions of TET Proteins and 5hmC Beyond DNA Demethylation

Role of Active DNA Demethylation in Neurological Disorders?

Concluding Remarks


Chapter 4. The Epigenetics of Parental Effects


Parent–Offspring Interactions and the Mental Health of the Offspring

Evolutionary Biology of Parental Signaling

The Biology of Parent Influences

Molecular Transduction of Maternal Signals

The Epigenetics of Parental Effects

Developmental Regulation of Hippocampal GR Expression in Humans

Reversibility of DNA Methylation

Non-Genomic Transmission of Traits from Parent to Offspring



Chapter 5. Epigenetic Mechanisms in Learning and Memory


Epigenetic Marks in the Nervous System and their Roles in Learning and Memory

How Does the Epigenetic Code Manifest as a Functional Change?

Epigenetically Based Disorders of Cognition and Novel Therapeutic Targets

Summary and Conclusions for Parts 1–3 of the Chapter

A Theoretical Framework for Epigenetic Mechanisms in Memory Formation and Storage

Summary and Conclusions – Cognitive Epigenetics



Chapter 6. Drug Addiction and Reward


Drug Addiction and Gene Transcription

Drugs and Neuronal Activation

Epigenetics of Addiction

Future Directions



Chapter 7. The Mind and its Nucleosomes – Chromatin (dys)Regulation in Major Psychiatric Disease

Introductory Remarks

Epigenetics in Psychiatry – Why Bother?

Epigenetic Alterations in Schizophrenia and Autism

Epigenetic Alterations in Mood and Anxiety Disorders, Including PTSD

Synopsis and Outlook



Chapter 8. HDAC Inhibitors as Novel Therapeutics in Aging and Alzheimer’s Disease

Aging, Alzheimer’s Disease, and Cognitive Decline

Gene Expression Dysregulation Associated with Age-Dependent Memory Impairment

Histone Acetylation Marks Associated with Memory

HDAC Proteins and Cognition

Classes of HDAC Inhibitors

HDAC Inhibitor Specificities

HDAC Inhibitor Brain Pharmacokinetics

HDAC Inhibitors and Histone Acetylation in Neurons

HDAC Inhibitors and Gene Transcription in Neurons

HDAC Inhibitors and Memory Formation

Non-Histone Targets of HDAC Inhibitors

Future HDAC Inhibitor Drug Design



Chapter 9. miRNAs and Neurodevelopmental Disorders


miRNA Biogenesis

miRNA Regulation of Cell Fates and Migration in the Developing Brain

miRNA Regulation of Neural Plasticity

Concluding Remarks


Chapter 10. Imprinting in the CNS and Neurodevelopmental Disorders

Imprinting and Neurodevelopmental Disorders

Genomic Imprinting

Mechanisms of Imprinting

Maternal and Paternal Genomes in Development

Neurodevelopmental Disorders of Imprinted Loci

Other Imprinted Genes and CNS Function



Chapter 11. Neuronal Genomic and Epigenetic Diversity


Mobile Elements in Mammalian Genomes

Host Defense

Somatic Mobile Element Activity

Genome Diversity Among Neurons

Additional Genomic Diversity Can Follow from Retrotransposon Activity

Nature, Nurture and Neuronal Genomes

How Do We Study Epigenetic Interactions with Neuronal Mosaicism?

Concluding Remarks



Chapter 12. Adult Neurogenesis


Epigenetic Control of NSCs: A Few Guiding Principles

Histone Modification

DNA Methylation

Regulatory Non-Coding RNAs and Chromatin Remodeling

Epigenetic Regulation of Adult Neurogenesis

NSC Self-Renewal and Maintenance of Quiescence

Proliferation of Transit-Amplifying Progenitors

Neuronal vs Glial Lineage Specification of Adult NSCs

Differentiation, Survival, and Maturation of Adult-Generated Neurons

Epigenetics, iPSCs, and Strategies for Neural Repair

Conclusions and Future Perspectives


Chapter 13. Transgenerational Inheritance in Mammals


Transgenerational Effects: Epidemiological and Laboratory Studies

Epigenetic Modifications and the Inheritance of Specific Traits

Transfer of Epigenetic Variation across Generations

Germline Transmission of Paternal Effects

Experience-Dependent Transfer through Females

Dissociating Paternal and Maternal Influences on Subsequent Generations

Future Directions in the Study of Epigenetics and Inheritance



Chapter 14. Epigenetics: Defining the Frontiers of Genomic Function

Epigenetics and Transcription: Cause or Consequence?

Implications of Epigenetics for Health Sciences





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© Academic Press 2013
8th February 2013
Academic Press
Hardcover ISBN:
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About the Editors

J. David Sweatt

J. David Sweatt

David Sweatt received a PhD in Pharmacology from Vanderbilt University for studies of intracellular signaling mechanisms. He then did a post-doctoral Fellowship at the Columbia University Center for Neurobiology and Behavior, working on memory mechanisms in the laboratory of Nobel laureate Eric Kandel. From 1989 to 2006 he was a member of the Neuroscience faculty at Baylor College of Medicine in Houston, Texas, rising through the ranks there to Professor and Director of the Neuroscience PhD program. In 2006 he moved to the University of Alabama at Birmingham where he served for ten years as the Evelyn F. McKnight endowed Chairman of the Department of Neurobiology at UAB Medical School, and the Director of the Evelyn F. McKnight Brain Institute at UAB. Dr. Sweatt’s laboratory studies biochemical mechanisms of learning and memory, most recently focusing on the role of epigenetic mechanisms in memory formation. In addition, his research program also investigates mechanisms of learning and memory disorders, such as intellectual disabilities, Alzheimer’s Disease, and aging-related memory dysfunction. He is currently the Allan D. Bass endowed Chairman of the Department of Pharmacology at Vanderbilt University Medical School, and has expanded his research program to include developing PharmacoEpigenetic approaches to enable new treatments for cognitive dysfunction. Dr. Sweatt has won numerous awards and honors, including an Ellison Medical Foundation Senior Scholar Award and election as a Fellow of the American Association for the Advancement of Science. In 2013 he won the Ipsen Foundation International Prize in Neural Plasticity, one of the most prestigious awards in his scientific field. In 2014 he was the recipient of the PROSE Award for the most outstanding reference volume published in 2013, for his book Epigenetic Mechanisms in the Nervous System. The book was also one of five finalists for the 2014 Dawkins Award for the most outstanding academic book published in 2013. In 2014, 2015, 2016, and 2017 Thomson-Reuters named him as a “Highly Cited Researcher” and as one of the “World’s Most Influential Scientific Minds.”

Affiliations and Expertise

McKnight Brain Institute, Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

Michael J. Meaney

Michael J. Meaney

Michael J Meaney is a James McGill Professor of Medicine at Douglas Mental health University Institute of McGill University. He is the Director of the Maternal Adversity, Vulnerability and Neurodevelopment Project and of the Developmental Neuroendocrinology Laboratory of McGill University. Meaney was educated at Loyola College of Montreal and received his PhD from Concordia University (Montreal) with post-doctoral training at The Rockefeller University in New York. Meaney’s primary research interest is that of the stable effects of early experience on gene expression and development. Meaney’s research is multidisciplinary and includes studies of behaviour and physiology, to molecular biology and genetics. The primary objective of these studies is to define the processes that govern gene – environment interactions. He has authored over 270 journal articles and has been the recipient of a Scientist Award from the Canadian Institutes for Health Research (CIHR) and a Distinguished Scientist Award from the National Alliance for Research in Schizophrenia and Affective Disorders. He was awarded Lougheed Prize (Alberta Heritage foundation for Medical Research), The Klerman Award (Cornell University), The Patricia Barchas Award (Research in Socio-physiology), The Heinz Lehman Award (Canadian College of Neuropsychopharmacology) and is the Bank of Montreal Fellow for the Canadian Institutes for Advanced Research. He currently holds a CIHR Senior Scientist Award. Graduates from Meaney’s lab hold faculty appointments across North America, Asia and Europe, including Columbia University, Queen’s University, University of California at Berkley, University of British Columbia, University of Michigan, University of Pennsylvania, and the RIKEN Institute of Japan. Research in the Meaney lab is funded by grants from Canadian (CIHR, NSERC), American (NIMH, NICDH) and International (HFSP) agencies.

Affiliations and Expertise

Douglas Institute, McGill University, Montreal, Canada

Eric Nestler

Eric Nestler

Dr. Nestler is the Nash Family Professor of Neuroscience at the Mount Sinai School of Medicine in New York, where he serves as Chair of the Department of Neuroscience and Director of the Friedman Brain Institute. He received his B.A., Ph.D., and M.D. degrees, and psychiatry residency training, from Yale University. He served on the Yale faculty from 1987-2000, where he was the Elizabeth Mears and House Jameson Professor of Psychiatry and Neurobiology, and Director of the Division of Molecular Psychiatry. He moved to Dallas in 2000 where he served as the Lou and Ellen McGinley Distinguished Professor and Chair of the Department of Psychiatry at The University of Texas Southwestern Medical Center until moving to New York in 2008. Dr. Nestler is a member of the Institute of Medicine and a Fellow of the American Academy of Arts and Sciences. The goal of Dr. Nestler’s research is to better understand the molecular mechanisms of addiction and depression based on work in animal models, and to use this information to develop improved treatments of these disorders.

Affiliations and Expertise

Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York, USA

Schahram Akbarian

Schahram Akbarian

Schahram Akbarian studied medicine at the Freie Universitaet Berlin, Germany. He is a board certified psychiatrist and molecular neuroscientist who trained at the Massachusetts General Hospital in Boston, the Whitehead Institute for Biomedical Research in Cambridge and the University of California at Irvine. In 2002, he joined the University of Massachusetts Medical School in Worcester where he established a research program in psychiatric epigenetics and served as the Director of the Brudnick Neuropsychiatric Research Institute. Presently, he heads the Division of Psychiatric Epigenomics in the Departments of Psychiatry and Neuroscience at Mount Sinai School of Medicine. He is a former recipient of the Klerman award from the Brain & Behavior Research Foundation, the Judith Silver Memorial award of the National Alliance for the Mentally Ill, the Outstanding resident award of the National Institute of Mental Health, and the Eva King Killam Award for Outstanding Translational Research, American College of Neuropsychopharmacology.

Dr. Akbarian has been a principal investigator on National Institutes of Health-funded research projects since 2001and published close to 100 articles in scientific journals and book chapters. He is a member of professional societies such as the American College of Neuropsychopharmacology and presently serves on the Scientific Advisory Board of the Brain & Behavior Research Foundation and on Editorial Boards of various journals in the field

Affiliations and Expertise

Department of Psychiatry, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York, USA


2013 PROSE Awards - Winner, Single Volume Reference Works: Association of American Publishers, Epigenetic Regulation in the Nervous System: Basic Mechanisms and Clinical Impact
PROSE Award 2013, Reference Work, Single Volume /Science: Biomedicine and Neuroscience, American Association of Publishers

BMA Medical Book Awards 2014 - Highly Commended, Neurology, British Medical Association

BMA Medical Book Awards 2014 - First Prize, Neurology, British Medical Association

PROSE Award 2013, Best in Reference Works, American Association of Publishers


"The book is primarily intended for advanced undergraduates, graduate students, active researchers and physician-scientists newly interested in the emerging field….Sweatt is also responsible for the book’s extensive illustrations, which are copies of his paintings depicting the role of epigenetic processes in the brain, and relate to work under way in his lab."--UAB News online, February 25, 2013
"Sweatt, Meaney, Nestler, and Akbarian present the first foundational work to address molecular, cellular, behavioral, and clinical roles for epigenetic mechanisms in the nervous system…This unique book is targeted for physicians and scientists, as well as researchers and students."--Reference & Research Book News, October 2013

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