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Neuroepigenetics

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https://www.readbyqxmd.com/read/27634148/the-potential-of-epigenetics-in-stress-enhanced-fear-learning-models-of-ptsd
#1
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
#2
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
#3
Hsiao-Ying Wey, Tonya M Gilbert, Nicole R Zürcher, 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
#4
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...
August 3, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/26137640/-neurogenetics-and-neuroepigenetics
#12
REVIEW
E V Savvateeva-Popova, E A Nikitina, A V Medvedeva
"Genetics of behavior," or "Neurogenetics," is based on the evolutionary ideas of T. Dobzhansky on brain development and behavior. It continues with the "experimental genetics of higher nervous activity" of I. Pavlov and uses a comparative approach in the study of heredity and variation in behavioral manifestations, from Protozoa to humans. The study of the classical Pavlovian conditioned reflex in mutant Drosophila helped to identify the main types of memory and their evolutionary conservatism. Long-term memory defects are caused by mutations of the same genes as in mental, retardation in humans, when signaling cascades intersecting with the cAMP-dependent pathway are damaged...
May 2015: Genetika
https://www.readbyqxmd.com/read/25856479/seeking-a-roadmap-toward-neuroepigenetics
#13
Jaehoon Shin, Guo-li Ming, Hongjun Song
A group of papers investigates functional regulatory elements in genomes from human tissue samples and cell lines. What can neuroscientists learn from the gigantic data set and how will it affect the direction of neuroepigenetics?
April 8, 2015: Neuron
https://www.readbyqxmd.com/read/25844808/dose-dependent-effects-of-morphine-exposure-on-mrna-and-microrna-mir-expression-in-hippocampus-of-stressed-neonatal-mice
#14
Ryan M McAdams, Ronald J McPherson, Richard P Beyer, Theo K Bammler, Frederico M Farin, Sandra E Juul
Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR) expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were treated from postnatal day (P) 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip twice daily and then exposed to stress consisting of hypoxia (100% N2 1 min and 100% O2 5 min) followed by 2h maternal separation...
2015: PloS One
https://www.readbyqxmd.com/read/25744673/regulation-of-gene-expression-and-pain-states-by-epigenetic-mechanisms
#15
REVIEW
Sandrine M Géranton, Keri K Tochiki
The induction of inflammatory or neuropathic pain states is known to involve molecular activity in the spinal superficial dorsal horn and dorsal root ganglia, including intracellular signaling events which lead to changes in gene expression. These changes ultimately cause alterations in macromolecular synthesis, synaptic transmission, and structural architecture which support central sensitization, a process required for the establishment of long-term pain states. Epigenetic mechanisms are essential for long-term synaptic plasticity and modulation of gene expression...
2015: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/25642412/neuroepigenetic-regulation-of-pathogenic-memories
#16
Stephanie E Sillivan, Thomas Vaissière, Courtney A Miller
Our unique collection of memories determines our individuality and shapes our future interactions with the world. Remarkable advances into the neurobiological basis of memory have identified key epigenetic mechanisms that support the stability of memory. Various forms of epigenetic regulation at the levels of DNA methylation, histone modification, and non-coding RNAs (ncRNAs) can modulate transcriptional and translational events required for memory processes. By changing the cellular profile in the brain's emotional, reward, and memory circuits, these epigenetic modifications have also been linked to perseverant, pathogenic memories...
January 1, 2015: Neuroepigenetics
https://www.readbyqxmd.com/read/25432069/neuroepigenetics-introduction-to-the-special-issue-on-epigenetics-in-neurodevelopment-and-neurological-diseases
#17
EDITORIAL
Guo-li Ming
No abstract text is available yet for this article.
June 2015: Experimental Neurology
https://www.readbyqxmd.com/read/25410546/the-future-of-neuroepigenetics-in-the-human-brain
#18
REVIEW
Amanda Mitchell, Panos Roussos, Cyril Peter, Nadejda Tsankova, Schahram Akbarian
Complex mechanisms shape the genome of brain cells into transcriptional units, clusters of condensed chromatin, and many other features that distinguish between various cell types and developmental stages sharing the same genetic material. Only a few years ago, the field's focus was almost entirely on a single mark, CpG methylation; the emerging complexity of neuronal and glial epigenomes now includes multiple types of DNA cytosine methylation, more than 100 residue-specific posttranslational histone modifications and histone variants, all of which superimposed by a dynamic and highly regulated three-dimensional organization of the chromosomal material inside the cell nucleus...
2014: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/25364289/epigenetic-mechanisms-in-schizophrenia
#19
REVIEW
Schahram Akbarian
Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DMA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clues about mechanisms contributing to dysregulated expression of synaptic and metabolic genes in schizophrenia brain, including the potential links to the underlying genetic risk architecture and environmental exposures...
September 2014: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/25227252/epigenetic-contributions-to-cognitive-aging-disentangling-mindspan-and-lifespan
#20
REVIEW
Amy M Spiegel, Angila S Sewal, Peter R Rapp
Epigenetic modifications of chromatin structure provide a mechanistic interface for gene-environment interactions that impact the individualization of health trajectories across the lifespan. A growing body of research indicates that dysfunctional epigenetic regulation contributes to poor cognitive outcomes among aged populations. Here we review neuroepigenetic research as it relates to cognitive aging, focusing specifically on memory function mediated by the hippocampal system. Recent work that differentiates epigenetic contributions to chronological aging from influences on mindspan, or the preservation of normal cognitive abilities across the lifespan, is also highlighted...
October 2014: Learning & Memory
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