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https://www.readbyqxmd.com/read/28631231/2-3-dideoxycytidine-protects-dopaminergic-neurons-in-a-mouse-model-of-parkinson-s-disease
#1
Jianyi Niu, Jing Xiong, Dan Hu, Fei Zeng, Shuke Nie, Shanping Mao, Tao Wang, Zhentao Zhang, Zhaohui Zhang
DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP(+)). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay...
June 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28616777/differential-regulation-of-mecp2-phosphorylation-by-laminin-in-oligodendrocytes
#2
Zalak S Parikh, Ashutosh Tripathi, Prakash P Pillai
Oligodendrocytes (OLGs) are the myelinating cells of the central nervous system (CNS), and its proper differentiation is crucial for normal functioning of neurons. Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional methylated DNA binding protein; mutation of which causes Rett syndrome, a severe neurodevelopmental disorder. Previously, we reported that MeCP2 is expressed in all the stages of oligodendrocyte development, and also shown the role of MeCP2 as a transcription regulator of myelin genes in OLGs...
June 14, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28606110/a-c9orf72-bac-mouse-model-recapitulates-key-epigenetic-perturbations-of-als-ftd
#3
Rustam Esanov, Gabriela Toro Cabrera, Nadja S Andrade, Tania F Gendron, Robert H Brown, Michael Benatar, Claes Wahlestedt, Christian Mueller, Zane Zeier
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal and progressive neurodegenerative disorder with identified genetic causes representing a significant minority of all cases. A GGGGCC hexanucleotide repeat expansion (HRE) mutation within the C9ORF72 gene has recently been identified as the most frequent known cause of ALS. The expansion leads to partial heterochromatinization of the locus, yet mutant RNAs and dipeptide repeat proteins (DPRs) are still produced in sufficient quantities to confer neurotoxicity...
June 12, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28605464/strand-specific-cpg-hemimethylation-a-novel-epigenetic-modification-functional-for-genomic-imprinting
#4
Iris Patiño-Parrado, Álvaro Gómez-Jiménez, Noelia López-Sánchez, José M Frade
Imprinted genes are regulated by allele-specific differentially DNA-methylated regions (DMRs). Epigenetic methylation of the CpGs constituting these DMRs is established in the germline, resulting in a 5-methylcytosine-specific pattern that is tightly maintained in somatic tissues. Here, we show a novel epigenetic mark, characterized by strand-specific hemimethylation of contiguous CpG sites affecting the germline DMR of the murine Peg3, but not Snrpn, imprinted domain. This modification is enriched in tetraploid cortical neurons, a cell type where evidence for a small proportion of formylmethylated CpG sites within the Peg3-controlling DMR is also provided...
June 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28597690/dna-methylation-and-copy-number-variation-analyses-of-human-embryonic-stem-cell-derived-neuroprogenitors-after-low-dose-decabromodiphenyl-ether-and-or-bisphenol-a-exposure
#5
L Du, W Sun, X M Li, X Y Li, W Liu, D Chen
The polybrominated diphenyl ether flame retardants decabromodiphenyl ether (BDE-209) and bisphenol A (BPA) are environmental contaminants that can cross the placenta and exert toxicity in the developing fetal nervous system. Copy number variants (CNVs) play a role in a number of genetic disorders and may be implicated in BDE-209/BPA teratogenicity. In this study, we found that BDE-209 and/or BPA exposure decreased neural differentiation efficiency of human embryonic stem cells (hESCs), although there was a >90% induction of neuronal progenitor cells (NPCs) from exposed hESCs...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28591654/hypoxia-epigenetically-confers-astrocytic-differentiation-potential-on-human-pluripotent-cell-derived-neural-precursor-cells
#6
Tetsuro Yasui, Naohiro Uezono, Hideyuki Nakashima, Hirofumi Noguchi, Taito Matsuda, Tomoko Noda-Andoh, Hideyuki Okano, Kinichi Nakashima
Human neural precursor cells (hNPCs) derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28591566/regulation-of-clustered-protocadherin-genes-in-individual-neurons
#7
REVIEW
Teruyoshi Hirayama, Takeshi Yagi
Individual neurons are basic functional units in the complex system of the brain. One aspect of neuronal individuality is generated by stochastic and combinatorial expression of diverse clustered protocadherins (Pcdhs), encoded by the Pcdha, Pcdhb, and Pcdhg gene clusters, that are critical for several aspects of neural circuit formation. Each clustered Pcdh gene has its own promoter containing conserved sequences and is transcribed by a promoter choice mechanism involving interaction between the promoter and enhancers...
June 4, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28585265/past-present-and-future-of-epigenetics-in-brain-sexual-differentiation
#8
REVIEW
Nancy G Forger
Sexual differentiation has long been considered "epigenetic," although the meaning of that word has shifted over time. Here we track the evolution of ideas about epigenetics in sexual differentiation, and identify principles that have emerged from recent studies. Experiments manipulating a particular epigenetic mechanism during neonatal life demonstrate a role for both histone acetylation and DNA methylation in the development of sex differences in the brain and behavior of rodents. In addition, hormone-dependent sex differences in the number of neurons of a particular phenotype may be programmed by differences in DNA methylation early in life...
June 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28577753/cocaine-induced-chromatin-modifications-associate-with-increased-expression-and-three-dimensional-looping-of-auts2
#9
Olivia Engmann, Benoit Labonté, Amanda Mitchell, Pavel Bashtrykov, Erin S Calipari, Chaggai Rosenbluh, Yong-Hwee E Loh, Deena M Walker, Dominika Burek, Peter J Hamilton, Orna Issler, Rachael L Neve, Gustavo Turecki, Yasmin Hurd, Andrew Chess, Li Shen, Isabelle Mansuy, Albert Jeltsch, Schahram Akbarian, Eric J Nestler
BACKGROUND: Exposure to drugs of abuse alters the epigenetic landscape of the brain's reward regions, such as the nucleus accumbens. We investigated how combinations of chromatin modifications affect genes that regulate responses to cocaine. We focused on Auts2, a gene linked to human evolution and cognitive disorders, which displays strong clustering of cocaine-induced chromatin modifications in this brain region. METHODS: We combined chromosome conformation capture, circularized chromosome conformation capture, and related approaches with behavioral paradigms relevant to cocaine phenotypes...
May 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28575645/tesc-gene-regulating-genetic-variant-rs7294919-affects-hippocampal-subfield-volumes-and-parahippocampal-cingulum-white-matter-integrity-in-major-depressive-disorder
#10
Kyu-Man Han, Eunsoo Won, June Kang, Sunyoung Choi, Aram Kim, Min-Soo Lee, Woo-Suk Tae, Byung-Joo Ham
Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919...
October 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28575429/evidence-that-a-sex-difference-in-neonatal-dna-methylation-organizes-two-distinct-phenotypic-characteristics-of-neurons-in-the-murine-forebrain
#11
https://www.readbyqxmd.com/read/28559115/methylation-dictates-pi-f-specific-cyp19-transcription-in-human-glial-cells
#12
Wenjuan Tan, Zhiping Zhu, Lan Ye, Lai K Leung
CYP19 is the single copy gene encoding for the estrogen synthetic enzyme aromatase. Alternate splicing of the promoter is the regulatory mechanism of this gene. In the brain, estrogen is synthesized in neuronal and glial cells and the gene is mainly regulated by the alternate promoter PI.f. The hormone produced in this vicinity has been associated with maintaining normal brain functions. Previously, epigenetic regulation has been shown in the promoters PII and I.3 of CYP19 in adipocytes. In the present study, the methylation of PI...
May 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28557603/genome-wide-methyl-seq-analysis-of-blood-brain-targets-of-glucocorticoid-exposure
#13
Fayaz Seifuddin, Gary Wand, Olivia Cox, Mehdi Pirooznia, Laura Moody, Xiaoju Yang, Jonathan Tai, Gretha Boersma, Kellie Tamashiro, Peter Zandi, Richard Lee
Chronic exposure to glucocorticoids (GCs) can lead to psychiatric complications through epigenetic mechanisms such as DNA methylation (DNAm). We sought to determine whether epigenetic changes in a peripheral tissue can serve as a surrogate for those in a relatively inaccessible tissue such as the brain. DNA extracted from the hippocampus and blood of mice treated with GCs or vehicle solution was assayed using a genome-wide DNAm platform (Methyl-Seq) to identify differentially methylated regions (DMRs) induced by GC treatment...
May 30, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28556790/dna-methylation-profiling-of-human-prefrontal-cortex-neurons-in-heroin-users-shows-significant-difference-between-genomic-contexts-of-hyper-and-hypomethylation-and-a-younger-epigenetic-age
#14
Alexey Kozlenkov, Andrew E Jaffe, Alisa Timashpolsky, Pasha Apontes, Sergei Rudchenko, Mihaela Barbu, William Byne, Yasmin L Hurd, Steve Horvath, Stella Dracheva
We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm) in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC) of heroin users who died from heroin overdose (N = 37), suicide completers (N = 22) with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28). We identified 1298 differentially methylated CpG sites (DMSs) between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0...
May 30, 2017: Genes
https://www.readbyqxmd.com/read/28552342/interplay-between-mitochondrial-metabolism-and-oxidative-stress-in-ischemic-stroke-an-epigenetic-connection
#15
REVIEW
Parimala Narne, Vimal Pandey, Prakash Babu Phanithi
The advent of epigenetics brought in a tectonic shift in the understanding of molecular basis of complex diseases like ischemic stroke (IS). Substantial scientific inquiry into the epigenetic basis of neurodegenerative diseases has bolstered the idea that altered carbon flux into central carbon metabolism and disturbed redox states govern the attendant transcriptional profiles through stochastic epigenetic changes. In view of an increasing understanding of the link between mitochondrial energy metabolism, oxidative stress and epigenetics in IS, the hitherto underappreciated 'neuroenergetics' is gaining sustained attention...
May 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28545252/cpg-and-non-cpg-methylation-in-epigenetic-gene-regulation-and-brain-function
#16
REVIEW
Hyun Sik Jang, Woo Jung Shin, Jeong Eon Lee, Jeong Tae Do
DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing or activation depending on the methylated regions. CpG and non-CpG methylation are found throughout the whole genome, including repetitive sequences, enhancers, promoters, and gene bodies. Interestingly, however, non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells...
May 23, 2017: Genes
https://www.readbyqxmd.com/read/28533418/hdac1-links-early-life-stress-to-schizophrenia-like-phenotypes
#17
Sanaz Bahari-Javan, Hristo Varbanov, Rashi Halder, Eva Benito, Lalit Kaurani, Susanne Burkhardt, Heike Anderson-Schmidt, Ion Anghelescu, Monika Budde, Roman M Stilling, Joan Costa, Juan Medina, Detlef E Dietrich, Christian Figge, Here Folkerts, Katrin Gade, Urs Heilbronner, Manfred Koller, Carsten Konrad, Sara Y Nussbeck, Harald Scherk, Carsten Spitzer, Sebastian Stierl, Judith Stöckel, Andreas Thiel, Martin von Hagen, Jörg Zimmermann, Antje Zitzelsberger, Sybille Schulz, Andrea Schmitt, Ivana Delalle, Peter Falkai, Thomas G Schulze, Alexander Dityatev, Farahnaz Sananbenesi, André Fischer
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28524415/ndrg4-an-early-detection-marker-for-colorectal-cancer-is-specifically-expressed-in-enteric-neurons
#18
N Vaes, M H F M Lentjes, M J Gijbels, G Rademakers, K L Daenen, W Boesmans, K A D Wouters, A Geuzens, X Qu, H P J Steinbusch, B P F Rutten, S H Baldwin, K A Sharkey, R M W Hofstra, M van Engeland, P Vanden Berghe, V Melotte
BACKGROUND: Promoter methylation of N-myc Downstream-Regulated Gene 4 (NDRG4) in fecal DNA is an established early detection marker for colorectal cancer (CRC). Despite its connection to CRC, NDRG4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole-body expression of NDRG4, with a focus on the intestinal tract. METHODS: We investigated NDRG4 expression throughout the body by immunohistochemistry, Western Blotting and in situ mRNA hybridization using tissues from NDRG4 wild-type, heterozygous and knockout mice and humans...
May 19, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28523552/epigenetics-of-huntington-s-disease
#19
Silvia Bassi, Takshashila Tripathi, Alan Monziani, Francesca Di Leva, Marta Biagioli
Huntington's disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957-961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971-983, 1993). The expanded CAG repeat, translated into a lengthened glutamine tract at the amino terminus of the huntingtin protein, affects its structural properties and functional activities...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523550/histone-posttranslational-modifications-in-schizophrenia
#20
Elizabeth A Thomas
Schizophrenia is a complex neuropsychiatric disorder with high heritability; however, family and twin studies have indicated that environmental factors also play important roles in the etiology of disease. Environmental triggers exert their influence on behavior via epigenetic mechanisms. Epigenetic modifications, such as histone acetylation and methylation, as well as DNA methylation, can induce lasting changes in gene expression and have therefore been implicated in promoting the behavioral and neuronal behaviors that characterize this disorder...
2017: Advances in Experimental Medicine and Biology
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