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Neuroepigenetics

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https://www.readbyqxmd.com/read/28638119/neuroimmunology-and-neuroepigenetics-in-the-establishment-of-sex-differences-in-the-brain
#1
REVIEW
Margaret M McCarthy, Bridget M Nugent, Kathryn M Lenz
The study of sex differences in the brain is a topic of neuroscientific study that has broad reaching implications for culture, society and biomedical science. Recent research in rodent models has led to dramatic shifts in our views of the mechanisms underlying the sexual differentiation of the brain. These include the surprising discoveries of a role for immune cells and inflammatory mediators in brain masculinization and a role for epigenetic suppression in brain feminization. How and to what degree these findings will translate to human brain development will be questions of central importance in future research in this field...
August 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28609483/histone-posttranslational-modifications-predict-specific-alternative-exon-subtypes-in-mammalian-brain
#2
Qiwen Hu, Eun Ji Kim, Jian Feng, Gregory R Grant, Elizabeth A Heller
A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addiction. It is now critical to develop highly innovative computational strategies to reveal the relevant regulatory transcriptional mechanisms that may underlie neuropsychiatric disease. We have analyzed chromatin regulation of alternative splicing, which is implicated in cocaine exposure in mice...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28523545/anxiety-and-epigenetics
#3
Andrew A Bartlett, Rumani Singh, Richard G Hunter
Anxiety disorders are highly prevalent psychiatric disorders often comorbid with depression and substance abuse. Twin studies have shown that anxiety disorders are moderately heritable. Yet, genome-wide association studies (GWASs) have failed to identify gene(s) significantly associated with diagnosis suggesting a strong role for environmental factors and the epigenome. A number of anxiety disorder subtypes are considered "stress related." A large focus of research has been on the epigenetic and anxiety-like behavioral consequences of stress...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28444216/dietary-metabolites-derived-from-gut-microbiota-critical-modulators-of-epigenetic-changes-in-mammals
#4
Mohd Iqbal Bhat, Rajeev Kapila
The mammalian gastrointestinal tract harbors trillions of commensal microorganisms, collectively known as the microbiota. The microbiota is a critical source of environmental stimuli and, thus, has a tremendous impact on the health of the host. The microbes within the microbiota regulate homeostasis within the gut, and any alteration in their composition can lead to disorders that include inflammatory bowel disease, allergy, autoimmune disease, diabetes, mental disorders, and cancer. Hence, restoration of the gut flora following changes or imbalance is imperative for the host...
May 1, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28220892/epigenetic-determinants-of-space-radiation-induced-cognitive-dysfunction
#5
Munjal M Acharya, Al Anoud D Baddour, Takumi Kawashita, Barrett D Allen, Amber R Syage, Thuan H Nguyen, Nicole Yoon, Erich Giedzinski, Liping Yu, Vipan K Parihar, Janet E Baulch
Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194101/contribution-of-neuroepigenetics-to-huntington-s-disease
#6
REVIEW
Laetitia Francelle, Caroline Lotz, Tiago Outeiro, Emmanuel Brouillet, Karine Merienne
Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28117018/editorial-thematic-issue-neuroepigenetics-and-neurodevelopmental-disorders-from-molecular-mechanisms-to-cell-fate-commitments-of-the-brain-cells-and-human-disease
#7
EDITORIAL
https://www.readbyqxmd.com/read/28044062/opening-up-the-dna-methylome-of-dementia
#8
R Delgado-Morales, M Esteller
Dementia is a complex clinical condition characterized by several cognitive impairments that interfere with patient independence in executing everyday tasks. Various neurodegenerative disorders have dementia in common among their clinical manifestations. In addition, these diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and frontotemporal dementia, share molecular alterations at the neuropathological level. In recent years, the field of neuroepigenetics has expanded massively and it is now clear that epigenetic processes, such as DNA methylation, are mechanisms involved in both normal and pathological brain function...
April 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27911745/the-role-of-epigenetic-mechanisms-in-the-regulation-of-gene-expression-in-the-nervous-system
#9
REVIEW
Justyna Cholewa-Waclaw, Adrian Bird, Melanie von Schimmelmann, Anne Schaefer, Huimei Yu, Hongjun Song, Ram Madabhushi, Li-Huei Tsai
Neuroepigenetics is a newly emerging field in neurobiology that addresses the epigenetic mechanism of gene expression regulation in various postmitotic neurons, both over time and in response to environmental stimuli. In addition to its fundamental contribution to our understanding of basic neuronal physiology, alterations in these neuroepigenetic mechanisms have been recently linked to numerous neurodevelopmental, psychiatric, and neurodegenerative disorders. This article provides a selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27634148/the-potential-of-epigenetics-in-stress-enhanced-fear-learning-models-of-ptsd
#10
Ashley M Blouin, Stephanie E Sillivan, Nadine F Joseph, Courtney A Miller
Prolonged distress and dysregulated memory processes are the core features of post-traumatic stress disorder (PTSD) and represent the debilitating, persistent nature of the illness. However, the neurobiological mechanisms underlying the expression of these symptoms are challenging to study in human patients. Stress-enhanced fear learning (SEFL) paradigms, which encompass both stress and memory components in rodents, are emerging as valuable preclinical models of PTSD. Rodent models designed to study the long-term mechanisms of either stress or fear memory alone have identified a critical role for numerous epigenetic modifications to DNA and histone proteins...
October 2016: Learning & Memory
https://www.readbyqxmd.com/read/27512601/cognitive-neuroepigenetics-the-next-evolution-in-our-understanding-of-the-molecular-mechanisms-underlying-learning-and-memory
#11
Paul Marshall, Timothy W Bredy
A complete understanding of the fundamental mechanisms of learning and memory continues to elude neuroscientists. Although many important discoveries have been made, the question of how memories are encoded and maintained at the molecular level remains. To date, this issue has been framed within the context of one of the most dominant concepts in molecular biology, the central dogma, and the result has been a protein-centric view of memory. Here we discuss the evidence supporting a role for neuroepigenetic mechanisms, which constitute dynamic and reversible, state-dependent modifications at all levels of control over cellular function, and their role in learning and memory...
2016: NPJ Science of Learning
https://www.readbyqxmd.com/read/27510902/insights-into-neuroepigenetics-through-human-histone-deacetylase-pet-imaging
#12
Hsiao-Ying Wey, Tonya M Gilbert, Nicole R Z├╝rcher, Angela She, Anisha Bhanot, Brendan D Taillon, Fredrick A Schroeder, Changing Wang, Stephen J Haggarty, Jacob M Hooker
Epigenetic dysfunction is implicated in many neurological and psychiatric diseases, including Alzheimer's disease and schizophrenia. Consequently, histone deacetylases (HDACs) are being aggressively pursued as therapeutic targets. However, a fundamental knowledge gap exists regarding the expression and distribution of HDACs in healthy individuals for comparison to disease states. Here, we report the first-in-human evaluation of neuroepigenetic regulation in vivo. Using positron emission tomography with [(11)C]Martinostat, an imaging probe selective for class I HDACs (isoforms 1, 2, and 3), we found that HDAC expression is higher in cortical gray matter than in white matter, with conserved regional distribution patterns within and between healthy individuals...
August 10, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27485392/toward-development-of-epigenetic-drugs-for-central-nervous-system-disorders-modulating-neuroplasticity-via-h3k4-methylation
#13
REVIEW
Emily L Ricq, Jacob M Hooker, Stephen J Haggarty
The mammalian brain dynamically activates or silences gene programs in response to environmental input and developmental cues. This neuroplasticity is controlled by signaling pathways that modify the activity, localization, and/or expression of transcriptional-regulatory enzymes in combination with alterations in chromatin structure in the nucleus. Consistent with this key neurobiological role, disruptions in the fine-tuning of epigenetic and transcriptional regulation have emerged as a recurrent theme in studies of the genetics of neurodevelopmental and neuropsychiatric disorders...
December 2016: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/27423867/current-proteomic-methods-to-investigate-the-dynamics-of-histone-turnover-in-the-central-nervous-system
#14
L A Farrelly, B D Dill, H Molina, M R Birtwistle, I Maze
Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover-the complete loss of old, and replacement by new, nucleosomal histones-is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues...
2016: Methods in Enzymology
https://www.readbyqxmd.com/read/26915423/drugging-the-methylome-dna-methylation-and-memory
#15
REVIEW
Andrew J Kennedy, J David Sweatt
Over the past decade, since epigenetic mechanisms were first implicated in memory formation and synaptic plasticity, dynamic DNA methylation reactions have been identified as integral to long-term memory formation, maintenance, and recall. This review incorporates various new findings that DNA methylation mechanisms are important regulators of non-Hebbian plasticity mechanisms, suggesting that these epigenetic mechanisms are a fundamental link between synaptic plasticity and metaplasticity. Because the field of neuroepigenetics is so young and the biochemical tools necessary to probe gene-specific questions are just now being developed and used, this review also speculates about the direction and potential of therapeutics that target epigenetic mechanisms in the central nervous system and the unique pharmacokinetic and pharmacodynamic properties that epigenetic therapies may possess...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/26868600/butyrate-neuroepigenetics-and-the-gut-microbiome-can-a-high-fiber-diet-improve-brain-health
#16
REVIEW
Megan W Bourassa, Ishraq Alim, Scott J Bultman, Rajiv R Ratan
As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite...
June 20, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/26818519/obesity-weighs-down-memory-through-a-mechanism-involving-the-neuroepigenetic-dysregulation-of-sirt1
#17
Frankie D Heyward, Daniel Gilliam, Mark A Coleman, Cristin F Gavin, Jing Wang, Garrett Kaas, Richard Trieu, John Lewis, Jerome Moulden, J David Sweatt
UNLABELLED: Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity...
January 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26804233/dissecting-structure-activity-relationships-of-crebinostat-brain-penetrant-hdac-inhibitors-for-neuroepigenetic-regulation
#18
Balaram Ghosh, Wen-Ning Zhao, Surya A Reis, Debasis Patnaik, Daniel M Fass, Li-Huei Tsai, Ralph Mazitschek, Stephen J Haggarty
Targeting chromatin-mediated epigenetic regulation has emerged as a potential avenue for developing novel therapeutics for a wide range of central nervous system disorders, including cognitive disorders and depression. Histone deacetylase (HDAC) inhibitors have been pursued as cognitive enhancers that impact the regulation of gene expression and other mechanisms integral to neuroplasticity. Through systematic modification of the structure of crebinostat, a previously discovered cognitive enhancer that affects genes critical to memory and enhances synaptogenesis, combined with biochemical and neuronal cell-based screening, we identified a novel hydroxamate-based HDAC inhibitor, here named neurinostat, with increased potency compared to crebinostat in inducing neuronal histone acetylation...
February 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26436772/correlating-gene-specific-dna-methylation-changes-with-expression-and-transcriptional-activity-of-astrocytic-kcnj10-kir4-1
#19
Sinifunanya E Nwaobi, Michelle L Olsen
DNA methylation serves to regulate gene expression through the covalent attachment of a methyl group onto the C5 position of a cytosine in a cytosine-guanine dinucleotide. While DNA methylation provides long-lasting and stable changes in gene expression, patterns and levels of DNA methylation are also subject to change based on a variety of signals and stimuli. As such, DNA methylation functions as a powerful and dynamic regulator of gene expression. The study of neuroepigenetics has revealed a variety of physiological and pathological states that are associated with both global and gene-specific changes in DNA methylation...
September 26, 2015: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/26290249/experience-modulates-the-effects-of-histone-deacetylase-inhibitors-on-gene-and-protein-expression-in-the-hippocampus-impaired-plasticity-in-aging
#20
Angila S Sewal, Holger Patzke, Evelyn J Perez, Pul Park, Elin Lehrmann, Yongqing Zhang, Kevin G Becker, Bonnie R Fletcher, Jeffrey M Long, Peter R Rapp
UNLABELLED: The therapeutic potential of histone deacetylase inhibitor (HDACi) treatment has attracted considerable attention in the emerging area of cognitive neuroepigenetics. The possibility that ongoing cognitive experience importantly regulates the cell biological effects of HDACi administration, however, has not been systematically examined. In an initial experiment addressing this issue, we tested whether water maze training influences the gene expression response to acute systemic HDACi administration in the young adult rat hippocampus...
August 19, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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