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Myelin regulatory factor

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https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#1
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28203609/zeb2-inhibiting-the-inhibitors-in-schwann-cells
#2
Bastian G Brinkmann, Susanne Quintes
Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28193689/signaling-by-fgf-receptor-2-not-fgf-receptor-1-regulates-myelin-thickness-through-activation-of-erk1-2-mapk-which-promotes-mtorc1-activity-in-an-akt-independent-manner
#3
M Furusho, A Ishii, R Bansal
FGF signaling has emerged as a significant 'late-stage' regulator of myelin thickness in the CNS, independent of oligodendrocyte differentiation. Therefore, it is critically important to identify the specific FGF-Receptor-type and its downstream signaling molecules in oligodendrocytes to obtain better insights into the regulatory mechanisms of myelin growth. Here, we show that FGF-Receptor-type-2 (FGFR2) is highly enriched at the paranodal loops of myelin. Conditional ablation of this receptor-type, but not FGF-Receptor-type-1 (FGFR1), resulted in attenuation of myelin growth, expression of major myelin genes, key transcription factor Myrf and ERK1/2 activity...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28130959/evidence-of-altered-brain-regulatory-gene-expression-in-tobacco-exposed-fetuses
#4
Hamisu M Salihu, Arnut Paothong, Rachita Das, Lindsey M King, Anupam Pradhan, Bridget Riggs, Eknath Naik, Erin M Siegel, Valerie E Whiteman
AIM: We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes. METHODS: At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN...
January 28, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28077718/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#5
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage-specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin-linked kinase (ILK) is an important protein that is expressed at the inner margins of the plasma membrane and can mediate some of these signals...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28065579/roles-of-regulatory-t-cells-and-il-10-in-virus-induced-demyelination
#6
REVIEW
Stanley Perlman, Jingxian Zhao
Neurotropic viruses are important causes of morbidity and mortality in human populations. Some of these viruses preferentially infect oligodendrocytes in the white matter, causing either direct lysis of infected cells, or more commonly myelin damage as a consequence of the host immune response to the virus. Virus-induced demyelination has similarities to the human disease multiple sclerosis. To study this disease process in experimental animals, mice are infected, most commonly, with neurotropic strains of mouse hepatitis virus, a coronavirus or Theiler's murine encephalomyelitis, a picornavirus...
January 4, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28051239/ex-vivo-expansion-of-antigen-specific-cd4-cd25-regulatory-t-cells-from-autologous-na%C3%A3-ve-cd4-t-cells-of-multiple-sclerosis-patients-as-a-potential-therapeutic-approach
#7
Y-J Xiang, M Ren, H Jiang, T-T Yang, Y He, D-H Ao, Y-Y Wang, Q Zhang, X-J He, X-G Gao, G-Z Liu
OBJECTIVE: CD4+CD25+ regulatory T cells (Tregs) have been found to have a decreased effector function in patients with multiple sclerosis (MS). In this study, we co-cultured naïve CD4+ T cells of MS patients with myelin basic protein (MBP)85-99 peptide as specific antigen and allogenic B cells as antigen-presenting cells, in an attempt to generate adequate antigen-specific CD4+CD25+ Tregs with normal or improved immune function. PATIENTS AND METHODS: Naïve CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) from patients with MS (n=5) and healthy controls (HC, n=5)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27973735/the-role-of-p38alpha-in-schwann-cells-in-regulating-peripheral-nerve-myelination-and-repair
#8
Sheridan L Roberts, Xin-Peng Dun, Gemma Dee, Bethany Gray, Thomas Mindos, David B Parkinson
Myelination in the peripheral nervous system (PNS) is controlled by both positive and negative regulators within Schwann cells to ensure timely onset and correct myelin thickness for saltatory conduction by neurons. Transcription factors such as Sox10, Oct6 and Krox20 form a positive regulatory network, whereas negative regulators such as cJun and Sox2 oppose myelination in Schwann cells. The role of the p38 mitogen activated protein kinase (MAPK) pathway has been studied in PNS myelination, but its precise function remains unclear, with both positive and negative effects of p38 activity reported upon both myelination and processes of nerve repair...
December 14, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27913589/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#9
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin linked kinase (ILK) is an important protein expressed at the inner margins of the plasma membrane, which can mediate some of these signals...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27889898/the-transcription-factors-ebf1-and-ebf2-are-positive-regulators-of-myelination-in-schwann-cells
#10
Diego Moruzzo, Lucilla Nobbio, Bruno Sterlini, G Giacomo Consalez, Fabio Benfenati, Angelo Schenone, Anna Corradi
Myelin formation by Schwann cells is tightly controlled by multiple pathways and regulatory molecules. The Ebf2 gene, belonging to the Ebf family of transcription factors regulating cell development and differentiation, is expressed in Schwann cells, and Ebf2 knockout mice show peripheral nerve defects. We also found that Ebf1 is expressed in Schwann cells. To investigate Ebf function in myelination, we silenced Ebf genes in myelinating dorsal root ganglia cultures. Combined downregulation of Ebf genes leads to a severe impairment of myelin formation that is completely rescued by their specific overexpression, suggesting that the expression level of Ebf genes strongly influences axon myelination...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27829268/altered-translational-control-of-fmrp-on-myelin-proteins-in-neuropsychiatric-disorders
#11
REVIEW
Se Jin Jeon, Jong Hoon Ryu, Geon Ho Bahn
Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ...
November 8, 2016: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27771555/srebf-2-polymorphism-influences-white-matter-microstructure-in-bipolar-disorder
#12
Sara Poletti, Veronica Aggio, Irene Bollettini, Andrea Falini, Cristina Colombo, Francesco Benedetti
The aim of the study is to investigate if gene polymorphisms in sterol regulatory element binding protein transcriptional factors SREBF-1 and SREBF-2, which regulate lipid and cholesterol metabolism, could affect white matter (WM) microstructure, the most recognized structural biomarker of bipolar disorder (BD). In a sample of 93 patients affected by BD, we investigated the effect of SREBF-1 rs11868035, and SREBF-2 rs1052717, on WM microstructure, using diffusion tensor imaging and tract-based spatial statistics...
October 15, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27733608/olig2-targeted-g-protein-coupled-receptor-gpr17-regulates-oligodendrocyte-survival-in-response-to-lysolecithin-induced-demyelination
#13
Zhimin Ou, Yuxia Sun, Li Lin, Nachun You, Xue Liu, Hongchao Li, Yanchen Ma, Lei Cao, Ying Han, Min Liu, Yaqi Deng, Luming Yao, Q Richard Lu, Ying Chen
: Demyelinating diseases, such as multiple sclerosis, are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination; however, the underlying molecular mechanisms remain unclear. Here, we performed genome occupancy analysis by chromatin immunoprecipitation sequencing in oligodendrocytes in response to lysolecithin-induced injury and found that Olig2 and its downstream target Gpr17 are critical factors in regulating oligodendrocyte survival. After injury to oligodendrocytes, Olig2 was significantly upregulated and transcriptionally targeted the Gpr17 locus...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27708418/b-cell-derived-transforming-growth-factor-%C3%AE-1-expression-limits-the-induction-phase-of-autoimmune-neuroinflammation
#14
Kristbjörg Bjarnadóttir, Mahdia Benkhoucha, Doron Merkler, Martin S Weber, Natalie L Payne, Claude C A Bernard, Nicolas Molnarfi, Patrice H Lalive
Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B-TGF-β1(-/-)) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG)...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27597394/progesterone-treatment-modulates-mrna-of-neurosteroidogenic-enzymes-in-a-murine-model-of-multiple-sclerosis
#15
Laura Garay, Paula Gonzalez Giqueaux, Rachida Guennoun, Michael Schumacher, Maria Claudia Gonzalez Deniselle, Alejandro F De Nicola
Previous studies of experimental autoimmune encephalomyelitis (EAE) have shown that progesterone decreases inflammatory cell infiltration and proinflammatory factors, increases myelination and attenuates clinical grade of EAE mice. To elucidate potential mediators of these effects, we analyzed the mRNA expression of neurosteroidogenic enzymes in the spinal cord, in view of the protective role of steroids in EAE. We also analyzed mitochondrial morphology and dynamics (fusion and fission proteins), considering the role of mitochondria in neurosteroidogenesis...
January 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27572856/immunopathophysiology-of-pediatric-cns-inflammatory-demyelinating-diseases
#16
Amit Bar-Or, Rogier Q Hintzen, Russell C Dale, Kevin Rostasy, Wolfgang Brück, Tanuja Chitnis
Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing...
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/27492885/genetic-evidence-for-a-role-of-the-srebp-transcription-system-and-lipid-biosynthesis-in-schizophrenia-and-antipsychotic-treatment
#17
Vidar M Steen, Silje Skrede, Tatiana Polushina, Miguel López, Ole A Andreassen, Johan Fernø, Stephanie Le Hellard
Schizophrenia is a serious psychotic disorder, with disabling symptoms and markedly reduced life expectancy. The onset is usually in late adolescence or early adulthood, which in time overlaps with the maturation of the brain including the myelination process. Interestingly, there seems to be a link between myelin abnormalities and schizophrenia. The oligodendrocyte-derived myelin membranes in the CNS are highly enriched for lipids (cholesterol, phospholipids and glycosphingolipids), thereby pointing at lipid homeostasis as a relevant target for studying the genetics and pathophysiology of schizophrenia...
August 1, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27466180/sox10-regulates-an-alternative-promoter-at-the-charcot-marie-tooth-disease-locus-mtmr2
#18
Elizabeth A Fogarty, Megan H Brewer, Jose F Rodriguez-Molina, William D Law, Ki H Ma, Noah M Steinberg, John Svaren, Anthony Antonellis
Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function. Loss-of-function mutations in the gene encoding myotubularin-related protein 2 (MTMR2) cause Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe demyelinating peripheral neuropathy characterized by myelin outfoldings along peripheral nerves...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27462272/activation-of-sterol-regulatory-element-binding-factors-by-fenofibrate-and-gemfibrozil-stimulates-myelination-in-zebrafish
#19
Yoshifumi Ashikawa, Yuhei Nishimura, Shiko Okabe, Shota Sasagawa, Soichiro Murakami, Mizuki Yuge, Koki Kawaguchi, Reiko Kawase, Toshio Tanaka
Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27455109/rapid-production-of-new-oligodendrocytes-is-required-in-the-earliest-stages-of-motor-skill-learning
#20
Lin Xiao, David Ohayon, Ian A McKenzie, Alexander Sinclair-Wilson, Jordan L Wright, Alexander D Fudge, Ben Emery, Huiliang Li, William D Richardson
We identified mRNA encoding the ecto-enzyme Enpp6 as a marker of newly forming oligodendrocytes, and used Enpp6 in situ hybridization to track oligodendrocyte differentiation in adult mice as they learned a motor skill (running on a wheel with unevenly spaced rungs). Within just 2.5 h of exposure to the complex wheel, production of Enpp6-expressing immature oligodendrocytes was accelerated in subcortical white matter; within 4 h, it was accelerated in motor cortex. Conditional deletion of myelin regulatory factor (Myrf) in oligodendrocyte precursors blocked formation of new Enpp6(+) oligodendrocytes and impaired learning within the same ∼2-3 h time frame...
September 2016: Nature Neuroscience
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