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neuronal epigenetics

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https://www.readbyqxmd.com/read/29456488/exploring-the-complexity-of-cortical-development-using-single-cell-transcriptomics
#1
REVIEW
Hyobin Jeong, Vijay K Tiwari
The developing neocortex in the mammalian brain is composed of multiple cell types including apical progenitors (AP), basal progenitors (BP), and neurons that populate three different layers, the ventricular zone (VZ), the subventricular zone (SVZ), and the cortical plate (CP). Despite recent advances, the diversity of the existing cell populations including those which are differentiating and mature, their biogenesis and the underlying gene regulatory mechanisms remain poorly known. Recent studies have taken advantage of the rapidly emerging single-cell technologies to decode the heterogeneity of cell populations at the transcriptome level during cortical development and their molecular details...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29451327/microrna-365-modulates-astrocyte-conversion-into-neuron-in-adult-rat-brain-after-stroke-by-targeting-pax6
#2
Jia-Lin Mo, Qi Liu, Zeng-Wei Kou, Kun-Wei Wu, Ping Yang, Xian-Hua Chen, Feng-Yan Sun
Reactive astrocytes induced by ischemia can transdifferentiate into mature neurons. This neurogenic potential of astrocytes may have therapeutic value for brain injury. Epigenetic modifications are widely known to involve in developmental and adult neurogenesis. PAX6, a neurogenic fate determinant, contributes to the astrocyte-to-neuron conversion. However, it is unclear whether microRNAs (miRs) modulate PAX6-mediated astrocyte-to-neuron conversion. In the present study we used bioinformatic approaches to predict miRs potentially targeting Pax6, and transient middle cerebral artery occlusion (MCAO) to model cerebral ischemic injury in adult rats...
February 16, 2018: Glia
https://www.readbyqxmd.com/read/29449454/deleting-hdac3-rescues-long-term-memory-impairments-induced-by-disruption-of-the-neuron-specific-chromatin-remodeling-subunit-baf53b
#3
Guanhua Shu, Enikö A Kramár, Alberto J López, Grace Huynh, Marcelo A Wood, Janine L Kwapis
Multiple epigenetic mechanisms, including histone acetylation and nucleosome remodeling, are known to be involved in long-term memory formation. Enhancing histone acetylation by deleting histone deacetylases, like HDAC3, typically enhances long-term memory formation. In contrast, disrupting nucleosome remodeling by blocking the neuron-specific chromatin remodeling subunit BAF53b impairs long-term memory. Here, we show that deleting HDAC3 can ameliorate the impairments in both long-term memory and synaptic plasticity caused by BAF53b mutation...
March 2018: Learning & Memory
https://www.readbyqxmd.com/read/29443015/isolation-and-cultivation-of-neural-progenitors-followed-by-chromatin-immunoprecipitation-of-histone-3-lysine-79-dimethylation-mark
#4
Patrick Bovio, Deborah Roidl, Stefanie Heidrich, Tanja Vogel, Henriette Franz
Brain development is a complex process, which is controlled in a temporo-spatial manner by gradients of morphogens and different transcriptional programs. Additionally, epigenetic chromatin modifications, like histone methylation, have an important role for establishing and maintaining specific cell fates within this process. The vast majority of histone methylation occurs on the flexible histone tail, which is accessible to histone modifiers, erasers, and histone reader proteins. In contrast, H3K79 methylation is located in the globular domain of histone 3 and is implicated in different developmental functions...
January 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29439356/frontal-cortex-epigenetic-dysregulation-during-the-progression-of-alzheimer-s-disease
#5
Laura Mahady, Muhammad Nadeem, Michael Malek-Ahmadi, Kewei Chen, Sylvia E Perez, Elliott J Mufson
Although the frontal cortex plays an important role in cognitive function and undergoes neuronal dysfunction in Alzheimer's disease (AD), the factors driving these cellular alterations remain unknown. Recent studies suggest that alterations in epigenetic regulation play a pivotal role in this process in AD. We evaluated frontal cortex histone deacetylase (HDAC) and sirtuin (SIRT) levels in tissue obtained from subjects with a premortem diagnosis of no-cognitive impairment (NCI), mild cognitive impairment (MCI), mild to moderate AD (mAD), and severe AD (sAD) using quantitative western blotting...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29438740/adult-hippocampal-mecp2-preserves-the-genomic-responsiveness-to-learning-required-for-long-term-memory-formation
#6
Kubra Gulmez Karaca, David V C Brito, Benjamin Zeuch, Ana M M Oliveira
MeCP2 is required both during postnatal neurodevelopment and throughout the adult life for brain function. Although it is well accepted that MeCP2 in the maturing nervous system is critical for establishing normal development, the functions of MeCP2 during adulthood are poorly understood. Particularly, the requirement of hippocampal MeCP2 for cognitive abilities in the adult is not studied. To characterize the role of MeCP2 in adult neuronal function and cognition, we used a temporal and region-specific disruption of MeCP2 expression in the hippocampus of adult male mice...
February 10, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29438503/lineage-specific-transcription-factors-and-epigenetic-regulators-mediate-tgf%C3%AE-dependent-enhancer-activation
#7
Raquel Fueyo, Simona Iacobucci, Stella Pappa, Conchi Estarás, Sergio Lois, Marta Vicioso-Mantis, Claudia Navarro, Sara Cruz-Molina, José Carlos Reyes, Álvaro Rada-Iglesias, Xavier de la Cruz, Marian A Martínez-Balbás
During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to which extent chromatin modifiers contribute to enhancer activity is starting to be uncovered. Here, we take advantage of neural stem cells as a model to unravel the mechanisms underlying neural enhancer activation in response to the TGFβ signaling...
February 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29435496/zika-virus-alters-dna-methylation-of-neural-genes-in-an-organoid-model-of-the-developing-human-brain
#8
Sylvie Janssens, Michael Schotsaert, Rahul Karnik, Vinod Balasubramaniam, Marion Dejosez, Alexander Meissner, Adolfo García-Sastre, Thomas P Zwaka
Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia...
January 2018: MSystems
https://www.readbyqxmd.com/read/29427507/epigenetic-modifications-insight-into-oligodendrocyte-lineage-progression-regeneration-and-disease
#9
REVIEW
Alexander Gregath, Richard Q Lu
Myelination by oligodendrocytes in the central nervous system permits high fidelity saltatory conduction from neuronal cell bodies to axon terminals. Dysmyelinating and demyelinating disorders impair normal nervous system functions. Consequently, an understanding of oligodendrocyte differentiation that moves beyond the genetic code into the field of epigenetics is essential. Chromatin reprogramming is critical for steering stage-specific differentiation processes during oligodendrocyte development. Fine temporal control of chromatin remodeling through ATP-dependent chromatin remodelers and sequential histone modifiers shapes a chromatin regulatory landscape conducive to oligodendrocyte fate specification, lineage differentiation, and maintenance of cell identity...
February 10, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29422978/dna-methylation-alterations-in-ipsc-and-hesc-derived-neurons-potential-implications-for-neurological-disease-modeling
#10
Laura de Boni, Gilles Gasparoni, Carolin Haubenreich, Sascha Tierling, Ina Schmitt, Michael Peitz, Philipp Koch, Jörn Walter, Ullrich Wüllner, Oliver Brüstle
Background: Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson's disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs)...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29412114/caveolin-1-in-stroke-neuropathology-and-neuroprotection-a-novel-molecular-therapeutic-target-for-ischemic-related-injury
#11
Shanshan Wang, Brian P Head
Cardiovascular disease and associated cerebral stroke are a global epidemic attributed to genetic and epigenetic factors, such as diet, life style and an increasingly sedentary existence due to technological advances in both the developing and developed world. There are approximately 5.9 million stroke-related deaths worldwide annually. Current epidemiological data indicate that nearly 16.9 million people worldwide suffer a new or recurrent stroke yearly. In 2014 alone, 2.4% of adults in the United States (U...
February 5, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29410282/osmotic-stress-induced-toxicity-exacerbates-parkinson-s-associated-effects-via-dysregulation-of-autophagy-in-transgenic-c-elegans-model
#12
Pooja Jadiya, Snober S Mir, Aamir Nazir
The accumulation of aggregate-prone proteins is a major representative of many neurological disorders, including Parkinson's disease (PD) wherein the cellular clearance mechanisms, such as the ubiquitin-proteasome and autophagy pathways are impaired. PD, known to be associated with multiple genetic and environmental factors, is characterized by the aggregation of α-synuclein protein and loss of dopaminergic neurons in midbrain. This disease is also associated with other cardiovascular ailments. Herein, we report our findings from studies on the effect of hyper and hypo-osmotic induced toxicity representing hyper and hypotensive condition as an extrinsic epigenetic factor towards modulation of Parkinsonism, using a genetic model Caenorhabditis elegans (C...
February 2, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29408968/microrna132-associated-multimodal-neuroimaging-patterns-in-unmedicated-major-depressive-disorder
#13
Shile Qi, Xiao Yang, Liansheng Zhao, Vince D Calhoun, Nora Perrone-Bizzozero, Shengfeng Liu, Rongtao Jiang, Tianzi Jiang, Jing Sui, Xiaohong Ma
There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons...
February 2, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29397557/targeting-histone-deacetylase-activity-to-arrest-cell-growth-and-promote-neural-differentiation-in-ewing-sarcoma
#14
Bárbara Kunzler Souza, Patrícia Luciana da Costa Lopez, Pâmela Rossi Menegotto, Igor Araujo Vieira, Nathalia Kersting, Ana Lúcia Abujamra, André T Brunetto, Algemir L Brunetto, Lauro Gregianin, Caroline Brunetto de Farias, Carol J Thiele, Rafael Roesler
There is an urgent need for advances in the treatment of Ewing sarcoma (EWS), an aggressive childhood tumor with possible neuroectodermal origin. Inhibition of histone deacetylases (HDAC) can revert aberrant epigenetic states and reduce growth in different experimental cancer types. Here, we investigated whether the potent HDAC inhibitor, sodium butyrate (NaB), has the ability to reprogram EWS cells towards a more differentiated state and affect their growth and survival. Exposure of two EWS cell lines to NaB resulted in rapid and potent inhibition of HDAC activity (1 h, IC50 1...
February 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29388081/loss-of-angelman-syndrome-protein-e6ap-disrupts-a-novel-antagonistic-estrogen-retinoic-acid-transcriptional-crosstalk-in-neurons
#15
Jimmy El Hokayem, Edwin Weeber, Zafar Nawaz
Angelman syndrome (AS) is a complex genetic disorder that affects the nervous system. AS affects an estimated 1 in 12,000 to 20,000 individuals. Characteristic features of AS includes developmental delay or intellectual disability, severe speech impairment, seizures, small head size (microcephaly), and problems with movement and balance (ataxia). AS individuals usually have microdeletion of the maternal copy of 15q11.2-15q13 region of chromosome 15. The E6-associated protein (E6AP, an E3 ubiquitin protein ligase enzyme) is encoded by the gene UBE3A, which is located in this region, and it has been shown that deregulation of E6AP gives rise to AS and neuropathology of autism spectrum disorders (ASDs) (e...
January 31, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29386386/de-novo-mutation-in-ring1-with-epigenetic-effects-on-neurodevelopment
#16
Sarah B Pierce, Mikaela D Stewart, Suleyman Gulsuner, Tom Walsh, Abhinav Dhall, Jon M McClellan, Rachel E Klevit, Mary-Claire King
RING1 is an E3-ubiquitin ligase that is involved in epigenetic control of transcription during development. It is a component of the polycomb repressive complex 1, and its role in that complex is to ubiquitylate histone H2A. In a 13-year-old girl with syndromic neurodevelopmental disabilities, we identified a de novo mutation, RING1 p.R95Q, which alters a conserved arginine residue in the catalytic RING domain. In vitro assays demonstrated that the mutant RING1 retains capacity to catalyze ubiquitin chain formation, but is defective in its ability to ubiquitylate histone H2A in nucleosomes...
January 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29383547/new-aspects-of-glioblastoma-multiforme-revealed-by-similarities-between-neural-and-glioblastoma-stem-cells
#17
REVIEW
Yoichiro Kawamura, Jun Takouda, Koji Yoshimoto, Kinichi Nakashima
Neural stem cells (NSCs) undergo self-renewal and generate neurons and glial cells under the influence of specific signals from surrounding environments. Glioblastoma multiforme (GBM) is a highly lethal brain tumor arising from NSCs or glial precursor cells owing to dysregulation of transcriptional and epigenetic networks that control self-renewal and differentiation of NSCs. Highly tumorigenic glioblastoma stem cells (GSCs) constitute a small subpopulation of GBM cells, which share several characteristic similarities with NSCs...
January 31, 2018: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29382156/alpha-secretase-adam10-regulation-insights-into-alzheimer-s-disease-treatment
#18
REVIEW
Rafaela Peron, Izabela Pereira Vatanabe, Patricia Regina Manzine, Antoni Camins, Márcia Regina Cominetti
ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer's disease (AD)...
January 29, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29378417/epigenetic-modifications-following-noxious-stimuli-in-infants
#19
Linda A Hatfield, Rebecca K Hoffman, Rosemary C Polomano, Yvette Conley
PURPOSE: To recruit healthy full- and preterm infants into genetic research and determine the effectiveness of a noninvasive DNA sampling technique for comparing epigenetic modifications. BACKGROUND: Noxious stimuli during a vulnerable period of infant neuronal plasticity may trigger long-term epigenetic changes affecting neurodevelopment, pain modulation, and reactivity. Recognizing epigenetic pain findings is problematic because parents are reluctant to enroll newborns into genetic research...
January 1, 2018: Biological Research for Nursing
https://www.readbyqxmd.com/read/29374200/interplay-between-tets-and-micrornas-in-the-adult-brain-for-memory-formation
#20
Eloïse A Kremer, Niharika Gaur, Melissa A Lee, Olivia Engmann, Johannes Bohacek, Isabelle M Mansuy
5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET) proteins. 5-hmC is widely present in the brain and is subjected to dynamic regulation during development and upon neuronal activity. It was recently shown to be involved in memory processes but currently, little is known about how it is controlled in the brain during memory formation. Here, we show that Tet3 is selectively up-regulated by activity in hippocampal neurons in vitro, and after formation of fear memory in the hippocampus...
January 26, 2018: Scientific Reports
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