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neuronal epigenetics

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https://www.readbyqxmd.com/read/29675472/low-input-and-multiplexed-microfluidic-assay-reveals-epigenomic-variation-across-cerebellum-and-prefrontal-cortex
#1
Sai Ma, Yuan-Pang Hsieh, Jian Ma, Chang Lu
Extensive effort is under way to survey the epigenomic landscape of primary ex vivo tissues to establish normal reference data and to discern variation associated with disease. The low abundance of some tissue types and the isolation procedure required to generate a homogenous cell population often yield a small quantity of cells for examination. This difficulty is further compounded by the need to profile a myriad of epigenetic marks. Thus, technologies that permit both ultralow input and high throughput are desired...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29670042/long-non-coding-rnas-in-neuronal-aging
#2
REVIEW
Diana Pereira Fernandes, Mainá Bitar, Frank M J Jacobs, Guy Barry
The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons...
April 18, 2018: Non-Coding RNA
https://www.readbyqxmd.com/read/29666508/intrinsic-mechanisms-of-neuronal-axon-regeneration
#3
REVIEW
Marcus Mahar, Valeria Cavalli
Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs...
April 17, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29666150/epigenetics-and-epitranscriptomics-in-temporal-patterning-of-cortical-neural-progenitor-competence
#4
REVIEW
Ki-Jun Yoon, Caroline Vissers, Guo-Li Ming, Hongjun Song
During embryonic brain development, neural progenitor/stem cells (NPCs) sequentially give rise to different subtypes of neurons and glia via a highly orchestrated process. To accomplish the ordered generation of distinct progenies, NPCs go through multistep transitions of their developmental competence. The molecular mechanisms driving precise temporal coordination of these transitions remains enigmatic. Epigenetic regulation, including changes in chromatin structures, DNA methylation, and histone modifications, has been extensively investigated in the context of cortical neurogenesis...
April 17, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29661885/the-long-non-coding-rna-paupar-promotes-kap1-dependent-chromatin-changes-and-regulates-olfactory-bulb-neurogenesis
#5
Ioanna Pavlaki, Farah Alammari, Bin Sun, Neil Clark, Tamara Sirey, Sheena Lee, Dan J Woodcock, Chris P Ponting, Francis G Szele, Keith W Vance
Many long non-coding RNAs (lncRNAs) are expressed during central nervous system (CNS) development, yet their in vivo roles and mechanisms of action remain poorly understood. Paupar , a CNS-expressed lncRNA, controls neuroblastoma cell growth by binding and modulating the activity of transcriptional regulatory elements in a genome-wide manner. We show here that the Paupar lncRNA directly binds KAP1, an essential epigenetic regulatory protein, and thereby regulates the expression of shared target genes important for proliferation and neuronal differentiation...
April 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29656664/epigenetic-aging-in-major-depressive-disorder
#6
Laura K M Han, Moji Aghajani, Shaunna L Clark, Robin F Chan, Mohammad W Hattab, Andrey A Shabalin, Min Zhao, Gaurav Kumar, Lin Ying Xie, Rick Jansen, Yuri Milaneschi, Brian Dean, Karolina A Aberg, Edwin J C G van den Oord, Brenda W J H Penninx
OBJECTIVE: Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue. METHOD: DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety...
April 16, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29656244/human-organoid-cultures-transformative-new-tools-for-human-virus-studies
#7
REVIEW
Sasirekha Ramani, Sue E Crawford, Sarah E Blutt, Mary K Estes
Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host-microbe interactions. Here, we summarize recent developments in the use of organoids for studying human viral pathogens, including intestinal infections with human rotavirus, norovirus, enteroviruses and adenoviruses (intestinal organoids and enteroids), neuronal infections with Zika virus (cerebral organoids) and respiratory infections with respiratory syncytial virus in (lung bud organoids)...
April 12, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29653249/directing-neuronal-cell-fate-in-vitro-achievements-and-challenges
#8
REVIEW
R J M Riemens, D L van den Hove, M Esteller, R Delgado-Morales
Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations...
April 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29625060/de-novo-dna-methylation-marking-the-path-from-stem-cell-to-neural-fate
#9
Ayana Sawai, Jeremy S Dasen
DNA methylation is an epigenetic mark that plays pivotal roles in gene regulation, but its functions in neural fate decisions are poorly understood. In this issue of Cell Stem Cell, Ziller et al. (2018) show that the de novo methyltransferase Dnmt3a ensures efficient generation of motor neurons from stem cells.
April 5, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29616397/adenosine-augmentation-evoked-by-an-ent1-inhibitor-improves-memory-impairment-and-neuronal-plasticity-in-the-app-ps1-mouse-model-of-alzheimer-s-disease
#10
Chia-Chia Lee, Ching-Pang Chang, Chun-Jung Lin, Hsing-Lin Lai, Yu-Han Kao, Sin-Jhong Cheng, Hui-Mei Chen, Yu-Ping Liao, Emilie Faivre, Luc Buée, David Blum, Jim-Min Fang, Yijuang Chern
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and synaptic dysfunction. Adenosine is an important homeostatic modulator that controls the bioenergetic network in the brain through regulating receptor-evoked signaling pathways, bioenergetic machineries, and epigenetic-mediated gene regulation. Equilibrative nucleoside transporter 1 (ENT1) is a major adenosine transporter that recycles adenosine from the extracellular space. In the present study, we report that a small adenosine analogue (designated J4) that inhibited ENT1 prevented the decline in spatial memory in an AD mouse model (APP/PS1)...
April 4, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29615864/molecular-neuropathology-of-astrocytes-and-oligodendrocytes-in-alcohol-use-disorders
#11
REVIEW
José J Miguel-Hidalgo
Postmortem studies reveal structural and molecular alterations of astrocytes and oligodendrocytes in both the gray and white matter (GM and WM) of the prefrontal cortex (PFC) in human subjects with chronic alcohol abuse or dependence. These glial cellular changes appear to parallel and may largely explain structural and functional alterations detected using neuroimaging techniques in subjects with alcohol use disorders (AUDs). Moreover, due to the crucial roles of astrocytes and oligodendrocytes in neurotransmission and signal conduction, these cells are very likely major players in the molecular mechanisms underpinning alcoholism-related connectivity disturbances between the PFC and relevant interconnecting brain regions...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29614314/glun2b-camkii-mediates-cfa-induced-hyperalgesia-via-hdac4-modified-spinal-cox2-transcription
#12
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, Gin-Den Chen, Dylan Chou, Ting Ruan, An-Sheng Lee, Hsueh-Hsiao Wang, Yat-Pang Chau, Hsien-Yu Peng, Cheng-Hung Lai
Histone deacetylase 4 (HDAC4), which actively shuttles between the nucleus and cytoplasm, is an attractive candidate for a repressor mechanism in epigenetic modification. However, the potential role of HDAC4-dependent epigenetics in the neural plasticity underlying the development of inflammatory pain has not been well established. By injecting complete Freund's adjuvant (CFA) into the hind-paw of Sprague-Dawley rats (200-250 g), we found animals displayed behavioral hyperalgesia was accompanied with HDAC4 phosphorylation and cytoplasmic redistribution in the dorsal horn neurons...
March 31, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29596946/genome-wide-dna-methylation-profiling-in-infants-born-to-gestational-diabetes-mellitus
#13
Xiaoling Weng, Fatao Liu, Hong Zhang, Mengyuan Kan, Ting Wang, Mingyue Dong, Yun Liu
BACKGROUND: Offspring exposed to gestational diabetes mellitus (GDM) are at a high risk for metabolic diseases. The mechanisms behind the association between offspring exposed to GDM in utero and an increased risk of health consequences later in life remain unclear. The aim of this study was to clarify the changes in methylation levels in the foetuses of women with GDM and to explore the possible mechanisms linking maternal GDM with a high risk of metabolic diseases in offspring later in life...
March 26, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29588251/effects-of-class-ii-selective-histone-deacetylase-inhibitor-on-neuromuscular-function-and-disease-progression-in-sod1-als-mice
#14
Daniela Buonvicino, Roberta Felici, Giuseppe Ranieri, Riccardo Caramelli, Andrea Lapucci, Leonardo Cavone, Mirko Muzzi, Lorena Di Pietro, Camilla Bernardini, Clemens Zwergel, Sergio Valente, Antonello Mai, Alberto Chiarugi
Emerging evidence indicates that transcriptome alterations due to epigenetic deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase (HDAC) inhibitors delays ALS development in mice, but these compounds failed when tested in ALS patients. Possibly, lack of selectivity towards specific classes of HDACs weakens the therapeutic effects of pan-HDAC inhibitors. Here, we tested the effects of the HDAC Class II selective inhibitor MC1568 on disease evolution, motor neuron survival as well as skeletal muscle function in SOD1G93A mice...
March 24, 2018: Neuroscience
https://www.readbyqxmd.com/read/29587355/rationale-for-dietary-antioxidant-treatment-of-adhd
#15
REVIEW
Annelies A J Verlaet, Carlijn M Maasakkers, Nina Hermans, Huub F J Savelkoul
Increasing understanding arises regarding disadvantages of stimulant medication in children with ADHD (Attention-Deficit Hyperactivity Disorder). This review presents scientific findings supporting dietary antioxidant treatment of ADHD and describes substantial alterations in the immune system, epigenetic regulation of gene expression, and oxidative stress regulation in ADHD. As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation, as well as by neuronal oxidative damage and loss of normal cerebral functions...
March 24, 2018: Nutrients
https://www.readbyqxmd.com/read/29575035/microrna-expression-profiles-of-neural-stem-cells-following-valproate-inducement
#16
Hui He, Wen Li, Min Peng, Jianbing Qin, Jinhong Shi, Haoming Li, Meiling Tian, Xinhua Zhang, Guangming Lv, Guohua Jin
Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression...
March 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29573696/low-omega-6-omega-3-ratio-in-a-maternal-protein-deficient-diet-promotes-histone-3-changes-in-progeny-neural-cells-and-favors-leukemia-inhibitory-factor-gene-transcription
#17
Alinny Rosendo Isaac, Emerson Alexandre Neves da Silva, Rhowena Jane Barbosa de Matos, Ricielle Lopes Augusto, Giselle Machado Magalhães Moreno, Ingrid Prata Mendonça, Raphael Fabrício de Souza, Paulo Euzébio Cabral-Filho, Cláudio Gabriel Rodrigues, Catarina Gonçalves-Pimentel, Fabíola Lacerda, Maria Luisa Martins Alessio, Marcelo Cairrão Araujo Rodrigues, Belmira Lara da Silveira Andrade-da-Costa
Omega-3 (n-3) fatty acids modulate epigenetic changes critical to genesis and differentiation of neural cells. Conversely, maternal protein-malnutrition can negatively modify these changes. This study investigated whether a low n-6/n-3 ratio in a maternal diet could favor histone-3 (H3) modifications, gene transcription and differentiation in the offspring neural cells even under protein-deficiency. Female rats fed a control (Ct), or 3 types of multideficient diets differing in protein levels or linoleic/alpha-linolenic fatty acid ratios (RBD, RBD-C, RBD-SO) from 30 days prior to mating and during pregnancy...
February 13, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29568390/characterization-of-brain-tumor-initiating-cells-isolated-from-an-animal-model-of-cns-primitive-neuroectodermal-tumors
#18
Sergey Malchenko, Simone T Sredni, Jerusha Boyineni, Yingtao Bi, Naira V Margaryan, Maheedhara R Guda, Yulia Kostenko, Tadanori Tomita, Ramana V Davuluri, Kiran Velpula, Mary J C Hendrix, Marcelo B Soares
CNS Primitive Neuroectodermal tumors (CNS-PNETs) are members of the embryonal family of malignant childhood brain tumors, which remain refractory to current therapeutic treatments. Current paradigm of brain tumorigenesis implicates brain tumor-initiating cells (BTIC) in the onset of tumorigenesis and tumor maintenance. However, despite their significance, there is currently no comprehensive characterization of CNS-PNETs BTICs. Recently, we described an animal model of CNS-PNET generated by orthotopic transplantation of human Radial Glial (RG) cells - the progenitor cells for adult neural stem cells (NSC) - into NOD-SCID mice brain and proposed that BTICs may play a role in the maintenance of these tumors...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29567833/structural-basis-for-the-ability-of-mbd-domains-to-bind-methyl-cg-and-tg-sites-in-dna
#19
Ke Liu, Chao Xu, Ming Lei, Ally Yang, Peter Loppnau, Timothy R Hughes, Jinrong Min
Cytosine methylation is a well characterized epigenetic mark and occurs at both CG and non-CG sites in DNA. Both methylated CG (mCG)- and mCH (H = A, C, or T)-containing DNAs, especially mCAC-containing DNAs, are recognized by methyl-CpG-binding protein 2 (MeCP2) to regulate gene expression in neuron development. However, the molecular mechanism involved in the binding of methyl-CpG-binding domain (MBD) of MeCP2 to these different DNA motifs is unclear. Here, we systematically characterized the DNA-binding selectivity of the MBDs in MeCP2 and MBD1-4 with isothermal titration calorimetry-based binding assays, mutagenesis studies, and X-ray crystallography...
March 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29565038/gabaergic-inhibitory-neurons-as-therapeutic-targets-for-cognitive-impairment-in-schizophrenia
#20
REVIEW
Meng-Yi Xu, Albert H C Wong
Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing...
March 22, 2018: Acta Pharmacologica Sinica
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