Special Issue "Epigenetics, Environment, and Brain Disorders"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (15 November 2018).

Special Issue Editor

Prof. Dr. Marija Kundakovic
E-Mail Website
Guest Editor
Department of Biological Sciences, Fordham University, Bronx, New York, USA
Interests: epigenetic mechanisms in normal brain function, behavior and psychiatric disorders; environmental effects on the brain; brain sexual dimorphism; neuroendocrinology

Special Issue Information

Dear Colleagues,

In the last 15 years, the brain epigenome has emerged as a biological substrate through which environmental and genetic risk factors can interact to bring about brain disorders. Numerous studies have shown that epigenomes of brain cells are dynamic and responsive to environmental cues throughout life. Epigenetic gene regulation is essential for normal brain development and, therefore, epigenetic disruption early in life can lead to lasting consequences for brain function and behavior. The brain epigenome continues to be plastic in the adolescent period and adulthood, further providing a substrate through which environmental exposures can affect brain gene expression, structure, and function.  Although the current evidence strongly supports the epigenetic link between environmental risk factors and brain disorders, the issues of causality and underlying mechanisms have still to be addressed more thoroughly. In addition, many new issues in the neuroepigenetics field have recently been highlighted including: Sex-, brain region- and cell type-specificity; specific windows of exposure; the relevance of peripheral epigenetic markers for brain studies; cross-generational epigenetic effects. We invite investigators to contribute original research articles, review articles, or short commentaries that will further stimulate the development of this field and provide new ideas on how to use this knowledge to improve our understanding of brain disorders, their diagnosis, early interventions, and treatments. Both animal and human studies are encouraged. Potential topics for this Special Issue may include, but are not limited to:

  • effects of environmental exposures including stress, toxicants, drugs, nutrition, and viral infections on the brain epigenome and behavior throughout life;
  • sex-specific epigenetic (dys)regulation in the brain;
  • epigenome editing in the brain;
  • inter- and trans-generational epigenetic effects of environmental exposures of relevance to brain and behavior;
  • peripheral epigenetic markers of environmental exposures of relevance to neurodevelopment and adult-onset brain disorders;
  • new methods and recommendations for future studies in neuroepigenetics and environmental epigenetics;
  • epigenetic changes and mechanisms in brain disorders.

Prof. Dr. Marija Kundakovic
Guest Editor

Manuscript Submission Information

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Keywords

  • Epigenetics
  • DNA methylation
  • Histone modification
  • Chromatin
  • Environment
  • Stress
  • Toxicological exposures
  • Drugs of abuse
  • Brain disorders
  • Sex-specific

Published Papers (6 papers)

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Research

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Open AccessArticle
Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice
Genes 2019, 10(4), 274; https://doi.org/10.3390/genes10040274 - 04 Apr 2019
Abstract
Lead (Pb) exposure is associated with a wide range of neurological deficits. Environmental exposures may impact epigenetic changes, such as DNA methylation, and can affect neurodevelopmental outcomes over the life-course. Mating mice were obtained from a genetically invariant C57BL/6J background agouti viable yellow [...] Read more.
Lead (Pb) exposure is associated with a wide range of neurological deficits. Environmental exposures may impact epigenetic changes, such as DNA methylation, and can affect neurodevelopmental outcomes over the life-course. Mating mice were obtained from a genetically invariant C57BL/6J background agouti viable yellow Avy strain. Virgin dams (a/a) were randomly assigned 0 ppm (control), 2.1 ppm (low), or 32 ppm (high) Pb-acetate water two weeks prior to mating with male mice (Avy/a), and this continued through weaning. At age 10 months, cortex neuronal nuclei were separated with NeuN+ antibodies in male mice to investigate neuron-specific genome-wide promoter DNA methylation using the Roche NimbleGen Mouse 3x720K CpG Island Promoter Array in nine pooled samples (three per dose). Several probes reached p-value < 10−5, all of which were hypomethylated: 12 for high Pb (minimum false discovery rate (FDR) = 0.16, largest intensity ratio difference = −2.1) and 7 for low Pb (minimum FDR = 0.56, largest intensity ratio difference = −2.2). Consistent with previous results in bulk tissue, we observed a weak association between early-life exposure to Pb and DNA hypomethylation, with some affected genes related to neurodevelopment or cognitive function. Although these analyses were limited to males, data indicate that non-dividing cells such as neurons can be carriers of long-term epigenetic changes induced in development. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Review

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Open AccessReview
Sex Differences in the Epigenome: A Cause or Consequence of Sexual Differentiation of the Brain?
Genes 2019, 10(6), 432; https://doi.org/10.3390/genes10060432 - 07 Jun 2019
Abstract
Females and males display differences in neural activity patterns, behavioral responses, and incidence of psychiatric and neurological diseases. Sex differences in the brain appear throughout the animal kingdom and are largely a consequence of the physiological requirements necessary for the distinct roles of [...] Read more.
Females and males display differences in neural activity patterns, behavioral responses, and incidence of psychiatric and neurological diseases. Sex differences in the brain appear throughout the animal kingdom and are largely a consequence of the physiological requirements necessary for the distinct roles of the two sexes in reproduction. As with the rest of the body, gonadal steroid hormones act to specify and regulate many of these differences. It is thought that transient hormonal signaling during brain development gives rise to persistent sex differences in gene expression via an epigenetic mechanism, leading to divergent neurodevelopmental trajectories that may underlie sex differences in disease susceptibility. However, few genes with a persistent sex difference in expression have been identified, and only a handful of studies have employed genome-wide approaches to assess sex differences in epigenomic modifications. To date, there are no confirmed examples of gene regulatory elements that direct sex differences in gene expression in the brain. Here, we review foundational studies in this field, describe transcriptional mechanisms that could act downstream of hormone receptors in the brain, and suggest future approaches for identification and validation of sex-typical gene programs. We propose that sexual differentiation of the brain involves self-perpetuating transcriptional states that canalize sex-specific development. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Open AccessReview
Using Openly Accessible Resources to Strengthen Causal Inference in Epigenetic Epidemiology of Neurodevelopment and Mental Health
Genes 2019, 10(3), 193; https://doi.org/10.3390/genes10030193 - 01 Mar 2019
Abstract
The recent focus on the role of epigenetic mechanisms in mental health has led to several studies examining the association of epigenetic processes with psychiatric conditions and neurodevelopmental traits. Some studies suggest that epigenetic changes might be causal in the development of the [...] Read more.
The recent focus on the role of epigenetic mechanisms in mental health has led to several studies examining the association of epigenetic processes with psychiatric conditions and neurodevelopmental traits. Some studies suggest that epigenetic changes might be causal in the development of the psychiatric condition under investigation. However, other scenarios are possible, e.g., statistical confounding or reverse causation, making it particularly challenging to derive conclusions on causality. In the present review, we examine the evidence from human population studies for a possible role of epigenetic mechanisms in neurodevelopment and mental health and discuss methodological approaches on how to strengthen causal inference, including the need for replication, (quasi-)experimental approaches and Mendelian randomization. We signpost openly accessible resources (e.g., “MR-Base” “EWAS catalog” as well as tissue-specific methylation and gene expression databases) to aid the application of these approaches. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Open AccessReview
A Review of Epigenetics of PTSD in Comorbid Psychiatric Conditions
Genes 2019, 10(2), 140; https://doi.org/10.3390/genes10020140 - 13 Feb 2019
Cited by 2
Abstract
Post-traumatic stress disorder (PTSD) is an acquired psychiatric disorder with functionally impairing physiological and psychological symptoms following a traumatic exposure. Genetic, epigenetic, and environmental factors act together to determine both an individual’s susceptibility to PTSD and its clinical phenotype. In this literature review, [...] Read more.
Post-traumatic stress disorder (PTSD) is an acquired psychiatric disorder with functionally impairing physiological and psychological symptoms following a traumatic exposure. Genetic, epigenetic, and environmental factors act together to determine both an individual’s susceptibility to PTSD and its clinical phenotype. In this literature review, we briefly review the candidate genes that have been implicated in the development and severity of the PTSD phenotype. We discuss the importance of the epigenetic regulation of these candidate genes. We review the general epigenetic mechanisms that are currently understood, with examples of each in the PTSD phenotype. Our focus then turns to studies that have examined PTSD in the context of comorbid psychiatric disorders or associated social and behavioral stressors. We examine the epigenetic variation in cases or models of PTSD with comorbid depressive disorders, anxiety disorders, psychotic disorders, and substance use disorders. We reviewed the literature that has explored epigenetic regulation in PTSD in adverse childhood experiences and suicide phenotypes. Finally, we review some of the information available from studies of the transgenerational transmission of epigenetic variation in maternal cases of PTSD. We discuss areas pertinent for future study to further elucidate the complex interactions between epigenetic modifications and this complex psychiatric disorder. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
Open AccessReview
Animal Models and Their Contribution to Our Understanding of the Relationship Between Environments, Epigenetic Modifications, and Behavior
Genes 2019, 10(1), 47; https://doi.org/10.3390/genes10010047 - 15 Jan 2019
Cited by 1
Abstract
The use of non-human animals in research is a longstanding practice to help us understand and improve human biology and health. Animal models allow researchers, for example, to carefully manipulate environmental factors in order to understand how they contribute to development, behavior, and [...] Read more.
The use of non-human animals in research is a longstanding practice to help us understand and improve human biology and health. Animal models allow researchers, for example, to carefully manipulate environmental factors in order to understand how they contribute to development, behavior, and health. In the field of behavioral epigenetics such approaches have contributed novel findings of how the environment physically interacts with our genes, leading to changes in behavior and health. This review highlights some of this research, focused on prenatal immune challenges, environmental toxicants, diet, and early-life stress. In conjunction, we also discuss why animal models were integral to these discoveries and the translational relevance of these discoveries. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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Open AccessReview
Genomic Enhancers in Brain Health and Disease
Genes 2019, 10(1), 43; https://doi.org/10.3390/genes10010043 - 14 Jan 2019
Abstract
Enhancers are non-coding DNA elements that function in cis to regulate transcription from nearby genes. Through direct interactions with gene promoters, enhancers give rise to spatially and temporally precise gene expression profiles in distinct cell or tissue types. In the brain, the accurate [...] Read more.
Enhancers are non-coding DNA elements that function in cis to regulate transcription from nearby genes. Through direct interactions with gene promoters, enhancers give rise to spatially and temporally precise gene expression profiles in distinct cell or tissue types. In the brain, the accurate regulation of these intricate expression programs across different neuronal classes gives rise to an incredible cellular and functional diversity. Newly developed technologies have recently allowed more accurate enhancer mapping and more sophisticated enhancer manipulation, producing rapid progress in our understanding of enhancer biology. Furthermore, identification of disease-linked genetic variation in enhancer regions has highlighted the potential influence of enhancers in brain health and disease. This review outlines the key role of enhancers as transcriptional regulators, reviews the current understanding of enhancer regulation in neuronal development, function and dysfunction and provides our thoughts on how enhancers can be targeted for technological and therapeutic goals. Full article
(This article belongs to the Special Issue Epigenetics, Environment, and Brain Disorders)
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