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https://www.readbyqxmd.com/read/28821749/dna-methylation-in-demyelinated-multiple-sclerosis-hippocampus
#1
Anthony M Chomyk, Christina Volsko, Ajai Tripathi, Sadie A Deckard, Bruce D Trapp, Robert J Fox, Ranjan Dutta
Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocampus. DNA methylation is a common epigenetic modifier of gene expression. In this study, we investigated whether DNA methylation is altered in MS hippocampus following demyelination. Our results show that mRNA levels of DNA methyltransferase were increased in demyelinated MS hippocampus, while de-methylation enzymes were decreased...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815487/benzophenone-3-impairs-autophagy-alters-epigenetic-status-and-disrupts-retinoid-x-receptor-signaling-in-apoptotic-neuronal-cells
#2
Agnieszka Wnuk, Joanna Rzemieniec, Władysław Lasoń, Wojciech Krzeptowski, Małgorzata Kajta
Benzophenone-3 (BP-3) is the most widely used compound among UV filters for the prevention of photodegradation. Population studies have demonstrated that it penetrates through the skin and crosses the blood-brain barrier. However, little is known about the impact of BP-3 on the nervous system and its possible adverse effects on the developing brain. We demonstrated that the neurotoxic effects of BP-3 were accompanied by the induction of apoptosis, as evidenced by apoptosis-related caspase-3 activation and apoptotic body formation as well as the inhibition of autophagy, as determined by the downregulation of autophagy-related genes, decreased autophagosome formation, and reduced LC3B-to-LC3A ratio...
August 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28801915/manganese-and-1-methyl-4-phenylpyridinium-mpp-induced-neurotoxicity-indicate-differences-in-morphological-electrophysiological-and-genome-wide-alterations-implications-for-idiopathic-parkinson-s-disease
#3
Rajeswara Babu Mythri, Narayana Reddy Raghunath, Santosh Chandrakant Narwade, Mirazkar DasharathaRao Pandareesh, Kollarkandi Rajesh Sabitha, Mohamad Aiyaz, Bipin Chand, Manas Sule, Krittika Ghosh, Senthil Kumar, Bhagyalakshmi Shankarappa, Soundarya Soundararajan, Phalguni Anand Alladi, Meera Purushottam, Narayanappa Gayathri, Deepti Dileep Deobagkar, Thenkanidiyoor Rao Laxmi, Srinivas Bharath Muchukunte Mukunda
Idiopathic Parkinson's disease (iPD) and manganese-induced atypical Parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the PD toxin 1-methyl-4-phenylpyridinium ion (MPP(+) ) and manganese (Mn) followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Mn mouse models...
August 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28801686/mir-12-and-mir-124-contribute-to-defined-early-phases-of-long-lasting-and-transient-memory
#4
Julia Michely, Susanne Kraft, Uli Müller
MicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in long-lasting synaptic plasticity and long-term memory (LTM). Since recent findings demonstrated a role of epigenetic regulation of gene expression in early memory phases we investigated whether epigenetic regulation by miRNAs also contributes to early memory phases. We used the olfactory associative learning paradigm in honeybees and addressed the contribution of miRNAs depending on the conditioning strength. We selected miR-12, miR-124, and miR-125 that have been implicated in processes of neuronal plasticity and analysed their contribution to non-associative and associative learning using miRNA inhibitors...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799488/environment-and-neurodegenerative-diseases-an-update-on-mirna-role
#5
Margherita Ferrante, Gea Oliveri Conti
INTRODUCTION: The importance of neurodegenerative diseases on the management of public health is growing and the real role of the environment and miRNA in their occurrence is still unclear. miRNA can affect significantly the regulatory network. The complex variety and gene-regulatory capacity of miRNAs is particularly valuable in the brain, being a very complex organ with a functional specialization of neurons highly adaptable to environmental stimuli. In particular a miRNAs role is demonstrated in neurological diseases as the effect to toxic and mutagenic substances exposure by the environment...
August 11, 2017: MicroRNA
https://www.readbyqxmd.com/read/28798132/single-cell-methylomes-identify-neuronal-subtypes-and-regulatory-elements-in-mammalian-cortex
#6
Chongyuan Luo, Christopher L Keown, Laurie Kurihara, Jingtian Zhou, Yupeng He, Junhao Li, Rosa Castanon, Jacinta Lucero, Joseph R Nery, Justin P Sandoval, Brian Bui, Terrence J Sejnowski, Timothy T Harkins, Eran A Mukamel, M Margarita Behrens, Joseph R Ecker
The mammalian brain contains diverse neuronal types, yet we lack single-cell epigenomic assays that are able to identify and characterize them. DNA methylation is a stable epigenetic mark that distinguishes cell types and marks regulatory elements. We generated >6000 methylomes from single neuronal nuclei and used them to identify 16 mouse and 21 human neuronal subpopulations in the frontal cortex. CG and non-CG methylation exhibited cell type-specific distributions, and we identified regulatory elements with differential methylation across neuron types...
August 11, 2017: Science
https://www.readbyqxmd.com/read/28798030/ethanol-exposure-regulates-gabra1-expression-via-histone-deacetylation-at-the-promoter-in-cultured-cortical-neurons
#7
John Peyton Bohnsack, Vraj K Patel, A Leslie Morrow
GABAA-Rs mediate the majority of inhibitory neurotransmission in the adult brain. α1-containing GABAA-Rs are the most prominent subtype in the adult brain, and are important in both homeostatic function and several disease pathologies including alcohol dependence, epilepsy, and stress. Ethanol exposure causes a decrease of α1 transcription and peptide expression both in vivo and in vitro, but the mechanism that controls the transcriptional regulation is unknown. Since ethanol is known to activate epigenetic regulation of gene expression, we tested the hypothesis that ethanol regulates α1 expression through histone modifications in cerebral cortical cultured neurons...
August 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28782640/effect-of-melatonin-on-neuronal-differentiation-requires-cbp-p300-mediated-acetylation-of-histone-h3-lysine-14
#8
Xian Li, Xueran Chen, Wenjuan Zhou, Shufang Ji, Xinyue Li, Guanchong Li, Guowei Liu, Fuwu Wang, Aijun Hao
The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties...
August 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28769976/new-insights-into-5hmc-dna-modification-generation-distribution-and-function
#9
REVIEW
Dong-Qiao Shi, Iftikhar Ali, Jun Tang, Wei-Cai Yang
Dynamic DNA modifications, such as methylation/demethylation on cytosine, are major epigenetic mechanisms to modulate gene expression in both eukaryotes and prokaryotes. In addition to the common methylation on the 5th position of the pyrimidine ring of cytosine (5mC), other types of modifications at the same position, such as 5-hydroxymethyl (5hmC), 5-formyl (5fC), and 5-carboxyl (5caC), are also important. Recently, 5hmC, a product of 5mC demethylation by the Ten-Eleven Translocation family proteins, was shown to regulate many cellular and developmental processes, including the pluripotency of embryonic stem cells, neuron development, and tumorigenesis in mammals...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28765641/hypomethylation-of-cntfr%C3%AE-is-associated-with-proliferation-and-poor-prognosis-in-lower-grade-gliomas
#10
Kun Fan, Xiaowen Wang, Jingwen Zhang, Romela Irene Ramos, Haibo Zhang, Chunjie Li, Dan Ye, Jiansheng Kang, Diego M Marzese, Dave S B Hoon, Wei Hua
Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28762874/reactivation-of-hyperglycemia-induced-hypocretin-hcrt-gene-silencing-by-n-acetyl-d-mannosamine-in-the-orexin-neurons-derived-from-human-ips-cells
#11
Koji Hayakawa, Yasuharu Sakamoto, Osamu Kanie, Atsuko Ohtake, Shusaku Daikoku, Yukishige Ito, Kunio Shiota
Orexin neurons regulate critical brain activities for controlling sleep, eating, emotions, and metabolism, and impaired orexin neuron function results in several neurological disorders. Therefore, restoring normal orexin function and understanding the mechanisms of loss or impairment of orexin neurons represent important goals. As a step toward that end, we generated human orexin neurons from induced pluripotent stem cells (hiPSCs) by treatment with N-acetyl-d-mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-O-GlcNAcylation on the HCRT gene locus, and, thereby, the treatment of inhibitors of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs...
August 1, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28761347/genetic-and-epigenetic-mechanisms-of-epilepsy-a-review
#12
REVIEW
Tian Chen, Mohan Giri, Zhenyi Xia, Yadu Nanda Subedi, Yan Li
Epilepsy is a common episodic neurological disorder or condition characterized by recurrent epileptic seizures, and genetics seems to play a key role in its etiology. Early linkage studies have localized multiple loci that may harbor susceptibility genes to epilepsy, and mutational analyses have detected a number of mutations involved in both ion channel and nonion channel genes in patients with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number variants at 2q24.2-q24.3, 7q11.22, 15q11...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28750583/association-of-a-history-of-child-abuse-with-impaired-myelination-in-the-anterior-cingulate-cortex-convergent-epigenetic-transcriptional-and-morphological-evidence
#13
Pierre-Eric Lutz, Arnaud Tanti, Alicja Gasecka, Sarah Barnett-Burns, John J Kim, Yi Zhou, Gang G Chen, Marina Wakid, Meghan Shaw, Daniel Almeida, Marc-Aurele Chay, Jennie Yang, Vanessa Larivière, Marie-Noël M'Boutchou, Léon C van Kempen, Volodymyr Yerko, Josée Prud'homme, Maria Antonietta Davoli, Kathryn Vaillancourt, Jean-François Théroux, Alexandre Bramoullé, Tie-Yuan Zhang, Michael J Meaney, Carl Ernst, Daniel Côté, Naguib Mechawar, Gustavo Turecki
OBJECTIVE: Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse. METHOD: Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed...
July 28, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28750017/corticotropin-releasing-factor-receptor-1-modulates-biomarkers-of-dna-oxidation-in-alzheimer-s-disease-mice
#14
Cheng Zhang, Robert A Rissman
Increased production of hydroxyl radical is the main source of oxidative damage in mammalian DNA that accumulates in Alzheimer's disease (AD). Reactive oxygen species (ROS) react with both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) to generate 8-hydroxy-2'-deoxyguanosine (8-OHdG), both of which can be measured in the urine. Knowledge of this pathway has positioned measurement of urine 8-OHdG as a reliable index of DNA oxidation and a potential biomarker target for tracking early cellular dysfunction in AD...
2017: PloS One
https://www.readbyqxmd.com/read/28746305/stimulation-of-functional-neuronal-regeneration-from-m%C3%A3-ller-glia-in-adult-mice
#15
Nikolas L Jorstad, Matthew S Wilken, William N Grimes, Stefanie G Wohl, Leah S VandenBosch, Takeshi Yoshimatsu, Rachel O Wong, Fred Rieke, Thomas A Reh
Many retinal diseases lead to the loss of retinal neurons and cause visual impairment. The adult mammalian retina has little capacity for regeneration. By contrast, teleost fish functionally regenerate their retina following injury, and Müller glia (MG) are the source of regenerated neurons. The proneural transcription factor Ascl1 is upregulated in MG after retinal damage in zebrafish and is necessary for regeneration. Although Ascl1 is not expressed in mammalian MG after injury, forced expression of Ascl1 in mouse MG induces a neurogenic state in vitro and in vivo after NMDA (N-methyl-d-aspartate) damage in young mice...
July 26, 2017: Nature
https://www.readbyqxmd.com/read/28743991/altered-visual-cortical-processing-in-a-mouse-model-of-mecp2-duplication-syndrome
#16
Dinghong Zhang, Bin Yu, Jing Liu, Weiqian Jiang, Taorong Xie, Ran Zhang, Dali Tong, Zilong Qiu, Haishan Yao
As an epigenetic modulator of gene expression, Methyl-CpG binding protein 2 (MeCP2) is essential for normal neurological function. Dysfunction of MeCP2 is associated with a variety of neurological disorders. MECP2 gene duplication in human causes neuropsychiatric symptoms such as mental retardation and autism. MeCP2 overexpression in mice results in neurobehavioural disorders, dendritic abnormalities, and synaptic defects. However, how gain of MeCP2 function influences cortical processing of sensory information remains unclear...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736194/the-epigenetic-drug-trichostatin-a-ameliorates-experimental-autoimmune-encephalomyelitis-via-t-cell-tolerance-induction-and-impaired-influx-of-t-cells-into-the-spinal-cord
#17
Arathi Jayaraman, Advait Soni, Bellur S Prabhakar, Mark Holterman, Sundararajan Jayaraman
Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization of myelin antigen-specific T lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment of NOD mice with the histone deacetylase inhibitor, Trichostatin A affords robust protection against myelin peptide induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis...
July 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28729685/nucleocytoplasmic-shuttling-of-histone-deacetylase-9-controls-activity-dependent-thalamocortical-axon-branching
#18
Ricardo Alchini, Haruka Sato, Naoyuki Matsumoto, Tomomi Shimogori, Noriyuki Sugo, Nobuhiko Yamamoto
During development, thalamocortical (TC) axons form branches in an activity-dependent fashion. Here we investigated how neuronal activity is converted to molecular signals, focusing on an epigenetic mechanism involving histone deacetylases (HDACs). Immunohistochemistry demonstrated that HDAC9 was translocated from the nucleus to the cytoplasm of thalamic cells during the first postnatal week in rats. In organotypic co-cultures of the thalamus and cortex, fluorescent protein-tagged HDAC9 also exhibited nuclueocytoplasmic translocation in thalamic cells during culturing, which was reversed by tetrodotoxin treatment...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723559/kmt2a-and-kmt2b-mediate-memory-function-by-affecting-distinct-genomic-regions
#19
Cemil Kerimoglu, M Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#20
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
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