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https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#1
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208729/altered-intracellular-milieu-of-adar2-deficient-motor-neurons-in-amyotrophic-lateral-sclerosis
#2
REVIEW
Takenari Yamashita, Megumi Akamatsu, Shin Kwak
Transactive response DNA-binding protein (TDP-43) pathology, and failure of A-to-I conversion (RNA editing) at the glutamine/arginine (Q/R) site of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of most patients with amyotrophic lateral sclerosis (ALS). Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes GluA2 Q/R site-RNA editing. Furthermore, conditional ADAR2 knockout mice (AR2) exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons, which is the most reliable pathological marker of ALS...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28205605/the-role-of-the-rna-demethylase-fto-fat-mass-and-obesity-associated-and-mrna-methylation-in-hippocampal-memory-formation
#3
Brandon J Walters, Valentina Mercaldo, Colleen J Gillon, Matthew Yip, Rachael L Neve, Frederick M Boyce, Paul W Frankland, Sheena A Josselyn
The formation of long-lasting memories requires coordinated changes in gene expression and protein synthesis (Davis and Squire, 1984; Duvarci et al, 2008; Hernandez and Abel, 2008). Although many studies implicate DNA modifications (DNA methylation, histone modifications) in memory formation, the contributions of RNA modifications remain largely unexplored. Here, we investigated the role of mRNA methylation in hippocampal-dependent memory formation in mice. RNA modifications are highly dynamic and readily reversible (Jia et al, 2013)...
February 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28203606/dna-methylation-in-oligodendroglial-cells-during-developmental-myelination-and-in-disease
#4
Sarah Moyon, Patrizia Casaccia
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28167242/epigenome-wide-dna-methylation-profiling-identifies-differential-methylation-biomarkers-in-high-grade-bladder-cancer
#5
Ekaterina Olkhov-Mitsel, Andrea J Savio, Ken J Kron, Vaijayanti V Pethe, Thomas Hermanns, Neil E Fleshner, Bas W van Rhijn, Theodorus H van der Kwast, Alexandre R Zlotta, Bharati Bapat
Epigenetic changes, including CpG island hypermethylation, occur frequently in bladder cancer (BC) and may be exploited for BC detection and distinction between high-grade (HG) and low-grade (LG) disease. Genome-wide methylation analysis was performed using Agilent Human CpG Island Microarrays to determine epigenetic differences between LG and HG cases. Pathway enrichment analysis and functional annotation determined that the most frequently methylated pathways in HG BC were enriched for anterior/posterior pattern specification, embryonic skeletal system development, neuron fate commitment, DNA binding, and transcription factor activity...
February 3, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28161254/pharmacological-inhibition-of-dna-methyltransferase-1-promotes-neuronal-differentiation-from-rodent-and-human-nasal-olfactory-stem-progenitor-cell-cultures
#6
I Franco, L Ortiz-López, B Roque-Ramírez, G B Ramírez-Rodríguez, M Lamas
Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2-P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs)...
February 1, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28155872/faithful-sgce-imprinting-in-ipsc-derived-cortical-neurons-an-endogenous-cellular-model-of-myoclonus-dystonia
#7
Karen Grütz, Philip Seibler, Anne Weissbach, Katja Lohmann, Francesca A Carlisle, Derek J Blake, Ana Westenberger, Christine Klein, Anne Grünewald
In neuropathology research, induced pluripotent stem cell (iPSC)-derived neurons are considered a tool closely resembling the patient brain. Albeit in respect to epigenetics, this concept has been challenged. We generated iPSC-derived cortical neurons from myoclonus-dystonia patients with mutations (W100G and R102X) in the maternally imprinted ε-sarcoglycan (SGCE) gene and analysed properties such as imprinting, mRNA and protein expression. Comparison of the promoter during reprogramming and differentiation showed tissue-independent differential methylation...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28152499/contributions-of-polyunsaturated-fatty-acids-pufa-on-cerebral-neurobiology-an-integrated-omics-approach-with-epigenomic-focus
#8
Nabarun Chakraborty, Seid Muhie, Raina Kumar, Aarti Gautam, Seshamalini Srinivasan, Bintu Sowe, George Dimitrov, Stacy-Ann Miller, Marti Jett, Rasha Hammamieh
The epigenetic landscape is vulnerable to diets. Here, we investigated the influence of different polyunsaturated fatty acids (PUFA) dietary supplements on rodents' nervous system development and functions and potential consequences to neurodegenerative disorders. Our previous nutrigenomics study showed significant impact of high n-3 PUFA-enriched diet (ERD) on synaptogenesis and various neuromodulators. The present study introduced a second equicaloric diet with n-6 PUFA balanced by n-3 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28149327/in-utero-exposure-to-maternal-smoking-is-associated-with-dna-methylation-alterations-and-reduced-neuronal-content-in-the-developing-fetal-brain
#9
Zac Chatterton, Brigham J Hartley, Man-Ho Seok, Natalia Mendelev, Sean Chen, Maria Milekic, Gorazd Rosoklija, Aleksandar Stankov, Iskra Trencevsja-Ivanovska, Kristen Brennand, Yongchao Ge, Andrew J Dwork, Fatemeh Haghighi
BACKGROUND: Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of cortical gray matter in childhood, indicating that prenatal exposure to tobacco may impact cortical development and manifest as behavioral problems. Cellular development is mediated by changes in epigenetic modifications such as DNA methylation, which can be affected by exposure to tobacco...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28137726/molecular-analyses-of-neurogenic-defects-in-a-human-pluripotent-stem-cell-model-of-fragile-x-syndrome
#10
Michael J Boland, Kristopher L Nazor, Ha T Tran, Attila Szücs, Candace L Lynch, Ryder Paredes, Flora Tassone, Pietro Paolo Sanna, Randi J Hagerman, Jeanne F Loring
New research suggests that common pathways are altered in many neurodevelopmental disorders including autism spectrum disorder; however, little is known about early molecular events that contribute to the pathology of these diseases. The study of monogenic, neurodevelopmental disorders with a high incidence of autistic behaviours, such as fragile X syndrome, has the potential to identify genes and pathways that are dysregulated in autism spectrum disorder as well as fragile X syndrome. In vitro generation of human disease-relevant cell types provides the ability to investigate aspects of disease that are impossible to study in patients or animal models...
January 29, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28132962/increased-expression-of-prion-protein-gene-is-accompanied-by-demethylation-of-cpg-sites-in-a-mouse-embryonal-carcinoma-cell-line-p19c6
#11
Wuyun Dalai, Eiko Matsuo, Natsumi Takeyama, Junichi Kawano, Keiichi Saeki
Elucidation of the processes regulating the prion protein gene (Prnp) is an important key to understanding the development of prion disorders. In this study, we explored the involvement of DNA methylation in Prnp transcriptional regulation during neuronal differentiation of embryonic carcinoma P19C6 cells. When P19C6 cells were differentiated into neuronal cells, the expression of Prnp was markedly increased, while CpG methylation was significantly demethylated at the nucleotide region between -599 and -238 from the transcription start site...
January 28, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28123699/epigenetic-control-of-cancer-by-neuropeptides
#12
Karina Galoian, Parthik Patel
Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions...
January 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28115522/the-5-hydroxymethylcytosine-5hmc-reader-uhrf2-is-required-for-normal-levels-of-5hmc-in-mouse-adult-brain-and-spatial-learning-and-memory
#13
Ruoyu Chen, Qiao Zhang, Xiaoya Duan, Philippe York, Guo-Dong Chen, Pengcheng Yin, Haijun Zhu, Meichen Xu, Peilin Chen, Qihan Wu, Dali Li, Jacques Samarut, Guoliang Xu, Pumin Zhang, Xiaohua Cao, Jiwen Li, Jiemin Wong
UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice Uhrf2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knockout mice are viable, fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain including cortex and hippocampus...
January 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28111355/epigenetics-in-epilepsy
#14
REVIEW
K Kobow, I Blümcke
Approximately 50 million people have epilepsy, making it the most common chronic and severe neurological disease worldwide, with increased risk of mortality and psychological and socioeconomic consequences impairing quality of life. More than 30% of patients with epilepsy have inadequate control of their seizures with drug therapy. Any structural brain lesion can provoke epilepsy. However, progression of seizure activity as well as the development of drug-resistance remains difficult to predict, irrespective of the underlying epileptogenic condition, i...
January 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28105729/whole-genome-grey-and-white-matter-dna-methylation-profiles-in-dorsolateral-prefrontal-cortex
#15
Jose Vicente Sanchez-Mut, Holger Heyn, Enrique Vidal, Raúl Delgado-Morales, Sebastian Moran, Sergi Sayols, Juan Sandoval, Isidre Ferrer, Manel Esteller, Johannes Gräff
The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood...
January 20, 2017: Synapse
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#16
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
: DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100736/methyl-cpg-binding-protein-mbd1-regulates-neuronal-lineage-commitment-through-maintaining-adult-neural-stem-cell-identity
#17
Emily M Jobe, Yu Gao, Brian E Eisinger, Janessa K Mladucky, Charles C Giuliani, Laurel E Kelnhofer, Xinyu Zhao
: Methyl-CpG-binding domain 1 (MBD1) belongs to a family of methyl-CpG-binding proteins that are epigenetic "readers" linking DNA methylation to transcriptional regulation. MBD1 is expressed in neural stem cells residing in the dentate gyrus of the adult hippocampus (aNSCs) and MBD1 deficiency leads to reduced neuronal differentiation, impaired neurogenesis, learning deficits, and autism-like behaviors in mice; however, the precise function of MBD1 in aNSCs remains unexplored. Here, we show that MBD1 is important for maintaining the integrity and stemness of NSCs, which is critical for their ability to generate neurons...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28065650/network-dynamics-mediate-circadian-clock-plasticity
#18
Abdelhalim Azzi, Jennifer A Evans, Tanya Leise, Jihwan Myung, Toru Takumi, Alec J Davidson, Steven A Brown
A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian "master clock," which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28030472/epigenetic-divergence-in-the-trpa1-promoter-correlates-with-pressure-pain-thresholds-in-healthy-individuals
#19
Sara Gombert, Mathias Rhein, Mirjam Eberhardt, Tino Münster, Stefan Bleich, Andreas Leffler, Helge Frieling
The expression pattern of important transduction molecules in nociceptive sensory neurons is likely to dictate pain sensitivity. While this notion is well established for increased pain sensitivities under conditions like inflammation and neuropathy, less is known as to which molecules are defining interindividual differences in pain sensitivity in healthy subjects. A genome-wide methylation analysis on monozygotic twins found that methylation of a CpG dinucleotide in the promoter of transient receptor potential ankyrin 1 (TRPA1) is inversely associated with the threshold for heat-induced pain...
December 22, 2016: Pain
https://www.readbyqxmd.com/read/28000730/an-acridine-derivative-4-5-bis-n-carboxy-methyl-imidazolium-methyl-acridine-dibromide-shows-anti-tdp-43-aggregation-effect-in-als-disease-models
#20
Archana Prasad, Gembali Raju, Vishwanath Sivalingam, Amandeep Girdhar, Meenakshi Verma, Abhishek Vats, Vibha Taneja, Ganesan Prabusankar, Basant K Patel
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with aggregation of TAR DNA-binding protein-43 (TDP-43) in neuronal cells and manifests as motor neuron dysfunction &muscle atrophy. The carboxyl-terminal prion-like domain of TDP-43 can aggregate in vitro into toxic β-sheet rich amyloid-like structures. So far, treatment options for ALS are very limited and Riluzole, which targets glutamate receptors, is the only but highly ineffective drug. Therefore, great interest exists in developing molecules for ALS treatment...
December 21, 2016: Scientific Reports
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