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https://www.readbyqxmd.com/read/29339171/dna-methylation-level-of-the-neprilysin-promoter-in-alzheimer-s-disease-brains
#1
Kenichi Nagata, Tatsuo Mano, Shigeo Murayama, Takaomi C Saido, Atsushi Iwata
Neprilysin (NEP), a membrane-bound metalloprotease, has been shown to play an essential role in the clearance of amyloid beta (Aβ) peptides. Previous studies have reported that NEP expression is downregulated in the normal aging brain as well as in the Alzheimer's disease (AD) brain, providing evidence that the downregulation of NEP expression contributes to the age-dependent deposition of Aβ-containing plaques, a pathological hallmark of AD. However, the mechanisms underlying the downregulation remain unclear...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29324752/tet-protein-function-during-drosophila-development
#2
Fei Wang, Svetlana Minakhina, Hiep Tran, Neha Changela, Joseph Kramer, Ruth Steward
The TET (Ten-eleven translocation) 1, 2 and 3 proteins have been shown to function as DNA hydroxymethylases in vertebrates and their requirements have been documented extensively. Recently, the Tet proteins have been shown to also hydroxylate 5-methylcytosine in RNA. 5-hydroxymethylcytosine (5hmrC) is enriched in messenger RNA but the function of this modification has yet to be elucidated. Because Cytosine methylation in DNA is barely detectable in Drosophila, it serves as an ideal model to study the biological function of 5hmrC...
2018: PloS One
https://www.readbyqxmd.com/read/29307297/sex-chromosome-contributions-to-sex-differences-in-multiple-sclerosis-susceptibility-and-progression
#3
Rhonda R Voskuhl, Amr H Sawalha, Yuichiro Itoh
BACKGROUND: Why are women more susceptible to multiple sclerosis, but men have worse disability progression? Sex differences in disease may be due to sex hormones, sex chromosomes, or both. OBJECTIVE: Determine whether differences in sex chromosomes can contribute to sex differences in multiple sclerosis using experimental autoimmune encephalomyelitis. METHODS: Sex chromosome transgenic mice, which permit the study of sex chromosomes not confounded by differences in sex hormones, were used to examine an effect of sex chromosomes on autoimmunity and neurodegeneration, focusing on X chromosome genes...
January 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29274882/neurodevelopment-and-behavior-in-neonatal-oxys-rats-with-genetically-determined-accelerated-senescence
#4
Tatyana N Igonina, Diana S Ragaeva, Maria A Tikhonova, Olga M Petrova, Yuri E Herbeck, Irina N Rozhkova, Tamara G Amstislavskaya, Sergey Ya Amstislavsky
Study of the developmental characteristics and mechanisms of senescence is an important field in brain aging research. The OXYS strain was selected from Wistar rats in Novosibirsk, and it serves as a rat model of accelerated aging. Previously, neurodegenerative processes and aberrant behavior were reported in experiments with adult OXYS rats. In our study, neurodevelopmental reflexes, neuronal density in the prefrontal cortex and hippocampus, and global DNA methylation in the hippocampus are compared between OXYS and WAG (Wistar Albino Glaxo) neonatal pups...
December 21, 2017: Brain Research
https://www.readbyqxmd.com/read/29251832/a-role-for-activity-dependent-epigenetics-in-the-development-and-treatment-of-major-depressive-disorder
#5
REVIEW
Corina Nagy, Kathryn Vaillancourt, Gustavo Turecki
Chronic stressors, during developmental critical periods and beyond, contribute to the risk of developing psychiatric conditions, including major depressive disorder (MDD). Epigenetic mechanisms including DNA methylation and histone modifications, at key stress response and neurotrophin genes, are increasingly implicated in mediating this risk. Although the exact mechanisms through which stressful environmental stimuli alter the epigenome are still unclear, research from the learning and memory fields indicates that epigenomic marks can be altered, at least in part, through calcium-dependent signalling cascades in direct response to neuronal activity...
December 18, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29239313/regulation-of-neuronal-survival-by-dna-methyltransferases
#6
REVIEW
Judit Symmank, Geraldine Zimmer
The limited regenerative capacity of neuronal cells requires tight orchestration of cell death and survival regulation in the context of longevity, age-associated diseases as well as during the development of the nervous system. Subordinate to genetic networks epigenetic mechanisms like DNA methylation and histone modifications are involved in the regulation of neuronal development, function and aging. DNA methylation by DNA methyltransferases (DNMTs), mostly correlated with gene silencing, is a dynamic and reversible process...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29228278/zinc-finger-protein-274-regulates-imprinted-expression-of-transcripts-in-prader-willi-syndrome-neurons
#7
Maéva Langouët, Heather R Glatt-Deeley, Michael S Chung, Clémence M Dupont-Thibert, Elodie Mathieux, Erin C Banda, Christopher E Stoddard, Leann Crandall, Marc Lalande
Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity and is caused by the absence of paternal contribution to chromosome 15q11-q13. Using induced pluripotent stem cell (iPSC) models of PWS, we previously discovered an epigenetic complex that is comprised of the zinc-finger protein ZNF274 and the SET domain bifurcated 1 (SETDB1) histone H3 lysine 9 (H3K9) methyltransferase and that silences the maternal alleles at the PWS locus. Here, we have knocked out ZNF274 and rescued the expression of silent maternal alleles in neurons derived from PWS iPSC lines, without affecting DNA methylation at the PWS-Imprinting Center (PWS-IC)...
December 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29223816/cortex-and-hippocampus-dna-epigenetic-response-to-a-long-term-arsenic-exposure-via-drinking-water
#8
Xiaoyan Du, Meiping Tian, Xiaoxue Wang, Jie Zhang, Qingyu Huang, Liangpo Liu, Heqing Shen
The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner...
December 7, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29213232/stress-induced-chronic-visceral-pain-of-gastrointestinal-origin
#9
REVIEW
Beverley Greenwood-Van Meerveld, Anthony C Johnson
Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS)...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#10
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155785/modeling-neuronal-death-and-degeneration-in-mouse-primary-cerebellar-granule-neurons
#11
Matthew Laaper, Takrima Haque, Ruth S Slack, Arezu Jahani-Asl
Cerebellar granule neurons (CGNs) are a commonly used neuronal model, forming an abundant homogeneous population in the cerebellum. In light of their post-natal development, abundance, and accessibility, CGNs are an ideal model to study neuronal processes, including neuronal development, neuronal migration, and physiological neuronal activity stimulation. In addition, CGN cultures provide an excellent model for studying different modes of cell death including excitotoxicity and apoptosis. Within a week in culture, CGNs express N-methyl-D-aspartate (NMDA) receptors, a specific ionotropic glutamate receptor with many critical functions in neuronal health and disease...
November 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155278/mecp2-expression-in-a-rat-model-of-risky-decision-making
#12
Jay V Deng, Caitlin A Orsini, Kristy G Shimp, Barry Setlow
Many neuropsychiatric disorders are associated with abnormal decision making involving risk of punishment, but the underlying molecular basis remains poorly understood. Methyl CpG-binding Protein 2 (MeCP2) is an epigenetic factor that regulates transcription by directly binding to methylated DNA. Here, we evaluated MeCP2 expression in the context of risk-taking behaviors using the Risky Decision-making Task (RDT), in which rats make discrete choices between a small "safe" food reward and a large "risky" food reward accompanied by varying probabilities of punishment...
November 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/29154458/epigenetic-mechanisms-of-major-depression-targeting-neuronal-plasticity
#13
REVIEW
Shusaku Uchida, Hirotaka Yamagata, Tomoe Seki, Yoshifumi Watanabe
Major depressive disorder is one of the most common mental illnesses as it affects more than 350 million people globally. Major depressive disorder is etiologically complex and disabling. Genetic factors play a role in the etiology of major depression. However, identical twin studies have shown high rates of discordance, indicating non-genetic mechanisms as well. For instance, stressful life events increase the risk of depression. Environmental stressors also induce stable changes in gene expression within the brain that may lead to maladaptive neuronal plasticity in regions implicated in disease pathogenesis...
November 20, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29145563/neuronal-dnmt1-deficiency-attenuates-diet-induced-obesity-in-mice
#14
Emily C Bruggeman, John T Garretson, Rui Wu, Hang Shi, Bingzhong Xue
Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development, but the role of neuronal DNA methyltransferases (Dnmts; enzymes that catalyze DNA methylation) in energy balance remains poorly understood. We investigated whether neuronal Dnmt1 regulates normal energy homeostasis and obesity development using a novel Dnmt1 knockout mouse model, Dnmt1fl/fl Synapsin1Cre (ND1KO), which specifically deletes Dnmt1 in neurons.Neuronal Dnmt1 deficiency reduced adiposity in chow-fed mice and attenuated obesity in HFD-fed male mice...
November 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/29134693/microglia-from-offspring-of-dams-with-allergic-asthma-exhibit-epigenomic-alterations-in-genes-dysregulated-in-autism
#15
Annie Vogel Ciernia, Milo Careaga, Janine M LaSalle, Paul Ashwood
Dysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain's resident immune cells...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29121802/hispolon-suppresses-lps-or-lta-induced-inos-no-production-and-apoptosis-in-bv-2-microglial-cells
#16
Ming-Shun Wu, Chih-Chiang Chien, Kur-Ta Cheng, Gottumukkala V Subbaraju, Yen-Chou Chen
Hispolon (HIS) is an active polyphenol compound derived from Phellinus linteus (Berkeley & Curtis), and our previous study showed that HIS effectively inhibited inflammatory responses in macrophages [Yang, L.Y., S.C. Shen, K.T. Cheng, G.V. Subbaraju, C.C. Chien and Y.C. Chen. Hispolon inhibition of inflammatory apoptosis through reduction of iNOS/NO production via HO-1 induction in macrophages. J. Ethnopharmacol. 156: 61-72, 2014]; however, its effect on neuronal inflammation is still undefined. In this study, HIS concentration- and time-dependently inhibited lipopolysaccharide (LPS)- and lipoteichoic acid (LTA)-induced inducible nitric oxide (NO) synthase (iNOS)/NO production with increased heme oxygenase (HO)-1 proteins in BV-2 microglial cells...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29111275/morphine-delays-neural-stem-cells-differentiation-by-facilitating-nestin-overexpression
#17
Ada Jimenez-Gonzalez, Adrián García-Concejo, Fernando León-Lobera, Raquel E Rodriguez
BACKGROUND: Morphine is used as an analgesic although it causes important secondary effects. These effects are triggered by several mechanisms leading to the dysregulation of gene expression. Here we aimed to study these alterations on neural stem cells (NSC) during CNS development. METHODS: AB strain and tg nestin:GFP zebrafish embryos, zebrafish primary neuron culture and mouse embryonic stem cells were used to assess the effect of morphine by qPCR, time lapse microscopy and western blot...
October 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29106556/location-matters-distinct-dna-methylation-patterns-in-gabaergic-interneuronal-populations-from-separate-microcircuits-within-the-human-hippocampus
#18
W Brad Ruzicka, Sivan Subburaju, Joseph T Coyle, Francine M Benes
Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors.The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects...
November 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29106553/genome-wide-dna-methylation-changes-associated-with-intermittent-explosive-disorder-a-gene-based-functional-enrichment-analysis
#19
Janitza L Montalvo-Ortiz, Huiping Zhang, Chao Chen, Chunyu Liu, Emil F Coccaro
Background: Intermittent explosive disorder (IED) is defined as a recurrent, problematic, and impulsive aggression that affects 3-4% of the U.S. population. While behavioral genetic studies report a substantial degree of genetic influence on aggression and impulsivity, epigenetic mechanisms underlying aggression and IED is not well known. Methods: The sample included 44 subjects (22 with a DSM-5 diagnosis of IED and 22 comparable subjects without IED). Peripheral blood DNA methylome was profiled using the Illumina Infinium HumanMethylation450 Beadchip...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29078406/site-directed-rna-repair-of-endogenous-mecp2-rna-in-neurons
#20
John R Sinnamon, Susan Y Kim, Glen M Corson, Zhen Song, Hiroyuki Nakai, John P Adelman, Gail Mandel
Rett syndrome (RTT) is a debilitating neurological disorder caused by mutations in the gene encoding the transcription factor Methyl CpG Binding Protein 2 (MECP2). A distinct disorder results from MECP2 gene duplication, suggesting that therapeutic approaches must restore close to normal levels of MECP2. Here, we apply the approach of site-directed RNA editing to repair, at the mRNA level, a disease-causing guanosine to adenosine (G > A) mutation in the mouse MeCP2 DNA binding domain. To mediate repair, we exploit the catalytic domain of Adenosine Deaminase Acting on RNA (ADAR2) that deaminates A to inosine (I) residues that are subsequently translated as G...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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