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https://www.readbyqxmd.com/read/28533418/hdac1-links-early-life-stress-to-schizophrenia-like-phenotypes
#1
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...
May 22, 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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28523544/drug-addiction-and-histone-code-alterations
#5
Hee-Dae Kim, Tanessa Call, Samantha Magazu, Deveroux Ferguson
Acute and prolonged exposure to drugs of abuse induces changes in gene expression, synaptic function, and neural plasticity in brain regions involved in reward. Numerous genes are involved in this process, and persistent changes in gene expression coincide with epigenetic histone modifications and DNA methylation. Histone modifications are attractive regulatory mechanisms, which can encode complex environmental signals in the genome of postmitotic cells, like neurons. Recently, it has been demonstrated that specific histone modifications are involved in addiction-related gene regulatory mechanisms, by a diverse set of histone-modifying enzymes and readers...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523538/mecp2-a-modulator-of-neuronal-chromatin-organization-involved-in-rett-syndrome
#6
Alexia Martínez de Paz, Juan Ausió
From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28516910/genetic-architecture-of-epigenetic-and-neuronal-ageing-rates-in-human-brain-regions
#7
Ake T Lu, Eilis Hannon, Morgan E Levine, Eileen M Crimmins, Katie Lunnon, Jonathan Mill, Daniel H Geschwind, Steve Horvath
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10(-20))...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515491/the-emerging-field-of-epigenetics-in-neurodegeneration-and-neuroprotection
#8
REVIEW
Jee-Yeon Hwang, Kelly A Aromolaran, R Suzanne Zukin
Epigenetic mechanisms - including DNA methylation, histone post-translational modifications and changes in nucleosome positioning - regulate gene expression, cellular differentiation and development in almost all tissues, including the brain. In adulthood, changes in the epigenome are crucial for higher cognitive functions such as learning and memory. Striking new evidence implicates the dysregulation of epigenetic mechanisms in neurodegenerative disorders and diseases. Although these disorders differ in their underlying causes and pathophysiologies, many involve the dysregulation of restrictive element 1-silencing transcription factor (REST), which acts via epigenetic mechanisms to regulate gene expression...
May 18, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28513272/neuronal-dna-methyltransferases-epigenetic-mediators-between-synaptic-activity-and-gene-expression
#9
Gonca Bayraktar, Michael R Kreutz
DNMT3A and 3B are the main de novo DNA methyltransferases (DNMTs) in the brain that introduce new methylation marks to non-methylated DNA in postmitotic neurons. DNA methylation is a key epigenetic mark that is known to regulate important cellular processes in neuronal development and brain plasticity. Accumulating evidence disclosed rapid and dynamic changes in DNA methylation of plasticity-relevant genes that are important for learning and memory formation. To understand how DNMTs contribute to brain function and how they are regulated by neuronal activity is a prerequisite for a deeper appreciation of activity-dependent gene expression in health and disease...
May 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28511916/pre-treatment-with-amitriptyline-causes-epigenetic-up-regulation-of-neuroprotection-associated-genes-and-has-anti-apoptotic-effects-in-mouse-neuronal-cells
#10
Nguyen Quoc Vuong Tran, An Nghia Nguyen, Kyoko Takabe, Zentaro Yamagata, Kunio Miyake
Antidepressants, such as imipramine and fluoxetine, are known to alter gene expression patterns by inducing changes in the epigenetic status of neuronal cells. There is also some evidence for the anti-apoptotic effect of various groups of antidepressants; however, this effect is complicated and cell-type dependent. Antidepressants of the tricyclic group, in particular amitriptyline, have been suggested to be beneficial in the treatment of neurodegenerative disorders. We examined whether amitriptyline exerts an anti-apoptotic effect via epigenetic mechanisms...
May 13, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28507584/effects-of-adenosine-receptor-antagonists-in-mptp-mouse-model-of-parkinson-s-disease-mitochondrial-dna-integrity
#11
Soha S Essawy, Mona Kamal Tawfik, Horya Erfan Korayem
INTRODUCTION: In Parkinson's disease (PD), compelling data indicate a functional link between adenosine/dopamine receptors and the progression of the neurodegenerative process. The present study was carried out to evaluate the effect of the non-selective adenosine receptor (ADR) antagonist caffeine, as well as the selective antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an ADRsA1 antagonist, and ((E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) (KW-6002), an ADRsA2A antagonist, on the prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in mice...
April 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28505093/the-crucial-role-of-dna-methylation-and-mecp2-in-neuronal-function
#12
REVIEW
Maria Fasolino, Zhaolan Zhou
A neuron is unique in its ability to dynamically modify its transcriptional output in response to synaptic activity while maintaining a core gene expression program that preserves cellular identity throughout a lifetime that is longer than almost every other cell type in the body. A contributing factor to the immense adaptability of a neuron is its unique epigenetic landscape that elicits locus-specific alterations in chromatin architecture, which in turn influences gene expression. One such epigenetic modification that is sensitive to changes in synaptic activity, as well as essential for maintaining cellular identity, is DNA methylation...
May 13, 2017: Genes
https://www.readbyqxmd.com/read/28502940/pet-imaging-of-18-f-fdg-11-c-methionine-11-c-flumazenil-and-11-c-4dst-in-progressive-multifocal-leukoencephalopathy
#13
Kenji Ishibashi, Yoshiharu Miura, Ken Matsumura, Yusuke Kanemasa, Kazuo Nakamichi, Masayuki Saijo, Jun Toyohara, Kenji Ishii
The use of positron emission tomography (PET) imaging in progressive multifocal leukoencephalopathy (PML) has rarely been reported. We herein report a set of PET images in a 63-year-old patient with PML. In PML lesions, the uptake of (18)F-fluorodeoxyglucose, (11)C-methionine, (11)C-flumazenil, and [methyl-(11)C]4'-thiothymidine was decreased, increased, decreased, and unchanged, respectively. These results suggest that glucose metabolism decreased, protein synthesis increased, neuronal integrity decreased, and the DNA synthesis and cellular proliferation of host cells were not activated in PML lesions...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28498846/mecp2-recognizes-cytosine-methylated-tri-nucleotide-and-di-nucleotide-sequences-to-tune-transcription-in-the-mammalian-brain
#14
Sabine Lagger, John C Connelly, Gabriele Schweikert, Shaun Webb, Jim Selfridge, Bernard H Ramsahoye, Miao Yu, Chuan He, Guido Sanguinetti, Lawrence C Sowers, Malcolm D Walkinshaw, Adrian Bird
Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG) is the classical MeCP2 DNA recognition sequence, but additional methylated sequence targets have been reported. Here we show by in vitro and in vivo analyses that MeCP2 binding to non-CG methylated sites in brain is largely confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in mouse brain is proportional to mCAC + mCG density and unexpectedly defines large genomic domains within which transcription is sensitive to MeCP2 occupancy...
May 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28494938/pi3k-akt-mtor-signaling-mediates-valproic-acid-induced-neuronal-differentiation-of-neural-stem-cells-through-epigenetic-modifications
#15
Xi Zhang, Xiaosong He, Qingqing Li, Xuejian Kong, Zhenri Ou, Le Zhang, Zhuo Gong, Dahong Long, Jianhua Li, Meng Zhang, Weidong Ji, Wenjuan Zhang, Liping Xu, Aiguo Xuan
Although valproic acid (VPA), has been shown to induce neuronal differentiation of neural stem cells (NSCs), the underlying mechanisms remain poorly understood. Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is involved in the neuronal differentiation of VPA-induced NSCs. Our data demonstrated that mTOR activation not only promoted but also was necessary for the neuronal differentiation of NSCs induced by VPA. We further found that inhibition of mTOR signaling blocked demethylation of neuron-specific gene neurogenin 1 (Ngn1) regulatory element in induced cells...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28492482/chromatin-switches-during-neural-cell-differentiation-and-their-dysregulation-by-prenatal-alcohol-exposure
#16
REVIEW
David P Gavin, Dennis R Grayson, Sajoy P Varghese, Marina Guizzetti
Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications...
May 11, 2017: Genes
https://www.readbyqxmd.com/read/28476540/epigenetic-and-transcriptional-modulation-of-wdr5-a-chromatin-remodeling-protein-in-huntington-s-disease-human-induced-pluripotent-stem-cell-hipsc-model
#17
Simona Baronchelli, Alberto La Spada, Aikaterini Ntai, Andrea Barbieri, Paola Conforti, Gloria Saccani Jotti, Serena Redaelli, Angela Bentivegna, Pasquale De Blasio, Ida Biunno
DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 differentially methylated regions (DMRs) at promoters in fully differentiated HD-hiPSCs. Subsequently, we focused on the methylation differences in a subcluster of genes related to Jumonji Domain Containing 3 (JMJD3), a demethylase that epigenetically regulates neuronal differentiation and activates neuronal progenitor associated genes, which are indispensable for neuronal fate acquisition...
May 2, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28461339/canonical-jak-stat-signaling-is-pivotal-for-long-term-depression-at-adult-hippocampal-temporoammonic-ca1-synapses
#18
Gemma McGregor, Andrew J Irving, Jenni Harvey
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is involved in numerous cellular processes and it is implicated in neurodegenerative disorders, like Alzheimer disease. Recent studies identified a crucial role for this pathway in activity-dependent long-term depression (LTD) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, it is unclear if JAK-STAT signaling also regulates excitatory synaptic function at the anatomically distinct temporoammonic (TA) input to CA1 neurons...
May 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28450074/structural-basis-of-mecp2-distribution-on-non-cpg-methylated-and-hydroxymethylated-dna
#19
M Jeannette Sperlazza, Stephanie M Bilinovich, Leander M Sinanan, Fatima R Javier, David C Williams
The Rett-syndrome-associated methyl-CpG-binding protein 2 (MeCP2) selectively binds methylated DNA to regulate transcription during the development of mature neurons. Like other members of the methyl-CpG-binding domain (MBD) family, MeCP2 functions through the recognition of symmetrical 5-methylcytosines in CpG (mCG) dinucleotides. Advances in base-level resolution epigenetic mapping techniques have revealed, however, that MeCP2 can bind asymmetrically methylated and hydroxymethylated CpA dinucleotides and that this alternative binding selectivity modifies gene expression in the developing mammalian brain...
April 24, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28444170/neuronal-activity-tgf%C3%AE-signaling-and-unpredictable-chronic-stress-modulate-transcription-of-gadd45-family-members-and-dna-methylation-in-the-hippocampus
#20
Daniela Grassi, Henriette Franz, Riccardo Vezzali, Patrick Bovio, Stefanie Heidrich, Fariba Dehghanian, Natalia Lagunas, Catherine Belzung, Kerstin Krieglstein, Tanja Vogel
Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB)...
April 21, 2017: Cerebral Cortex
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