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Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
Jennifer K Sabo, Vivi Heine, John C Silbereis, Lucas Schirmer, Steven W Levison, David H Rowitch
OBJECTIVE: Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic (HI) injury, the downstream functional targets are poorly understood. The basic helix-loop-helix protein, oligodendrocyte transcription factor 1 (Olig1), promotes oligodendrocyte (OL) development and is essential during remyelination in adult mice...
April 2017: Annals of Neurology
Christina Brill, Till Scheuer, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
The premature increase of oxygen tension may contribute to oligodendroglial precursor cell (OPC) damage in preterm infants. Fetal OPCs are exposed to low oxygen tissue tensions not matched when cells are cultured in room air. Maturation (A2B5, O4, O1, MBP, CNP, arborization), oxidative stress (nitrotyrosine Western blot, NRF2 and SOD2 expression), apoptosis (TUNEL), proliferation (Ki67), and expression of transcription factors regulated by Hypoxia-Inducible-Factor-1-alpha (Hif-1α) expressed in OPCs (Olig1, Olig2, Sox9, Sox10) were assessed in rat OPCs and OLN93 cells cultured at 5% O2 and 21% O2...
February 23, 2017: Scientific Reports
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. The current studies demonstrate that ILK deletion reduces the proliferation and differentiation of OPCs in the developing CNS...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tao Deng, Yuri Postnikov, Shaofei Zhang, Lillian Garrett, Lore Becker, Ildikó Rácz, Sabine M Hölter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Michael Bustin
An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination...
April 7, 2017: Nucleic Acids Research
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. The current studies demonstrate that ILK deletion reduces the proliferation and differentiation of OPCs in the developing CNS...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Masanao Ikeda, M Ibrahim Hossain, Li Zhou, Masao Horie, Kazuhiro Ikenaka, Arata Horii, Hirohide Takebayashi
Oligodendrocytes (OLs) are glial cells that form myelin sheaths surrounding the axons in the central nervous system (CNS). Jimpy (jp) mutant mice are dysmyelinating disease models that show developmental abnormalities in myelinated OLs in the CNS. The causative gene in jp mice is the proteolipid protein (PLP) located on the X chromosome. Mutations in the jp allele result in exon 5 skipping and expression of abnormal PLP containing a C-terminal frame shift. Many lines of evidence suggest that abnormal PLP in OLs results in endoplasmic reticulum (ER) stress and cell death...
November 25, 2016: Anatomical Science International
Francisca F Vasconcelos, Alessandro Sessa, Cátia Laranjeira, Alexandre A S F Raposo, Vera Teixeira, Daniel W Hagey, Diogo M Tomaz, Jonas Muhr, Vania Broccoli, Diogo S Castro
The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program...
October 4, 2016: Cell Reports
Ewa Ferensztajn-Rochowiak, Maciej Tarnowski, Jerzy Samochowiec, Michal Michalak, Mariusz Z Ratajczak, Janusz K Rybakowski
Neuroinflammation, with microglial activation as an important element, plays a role in the pathogenesis of bipolar disorder (BD). Also, in mood disorders, pathological changes have been demonstrated in macroglial cells, such as astrocyctes and oligodendrocytes. Postmortem brain studies of BD patients to assess glial cells, such as astrocytes and oligodendrocytes and their markers such as glial fibrillary acidic protein (GFAP), Olig1 and Olig2, produced controversial results. On the other hand, investigation of these markers in the peripheral blood of such patients has not been performed so far...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Jun Ju, Qian Liu, Yang Zhang, Yuanxiu Liu, Mei Jiang, Liguo Zhang, Xuelian He, Chenchen Peng, Tao Zheng, Q Richard Lu, Hedong Li
The oligodendrocyte transcription factor Olig2 plays a crucial role in the neurogenesis of both spinal cord and brain. In the cerebellum, deletion of both Olig2 and Olig1 results in impaired genesis of Purkinje cells (PCs) and Pax2(+) interneurons. Here, we perform an independent study to show that Olig2 protein is transiently expressed in the cerebellar ventricular zone (VZ) during a period when PCs are specified. Further analyses demonstrate that Olig2 is expressed in both cerebellar VZ progenitors and early-born neurons...
2016: Scientific Reports
Fraser I Young, Vsevolod Telezhkin, Sarah J Youde, Martin S Langley, Maria Stack, Paul J Kemp, Rachel J Waddington, Alastair J Sloan, Bing Song
Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells...
2016: Stem Cells International
Qi Qi, Yuxin Zhang, Lin Shen, Rui Wang, Jiansheng Zhou, Hezuo Lü, Jianguo Hu
PURPOSE: Our purpose was to systematically investigate the expression pattern and role of Olig1 in neural cells during rat spinal cord development. ANIMALS AND METHODS: Spinal cord tissues were dissected from Sprague-Dawley rats at embryonic day 14.5 (E14.5) and E18.5, postnatal day 0 (P0), P3, P7, postnatal 2 weeks (P2W), P4W, and adults (more than 2 months after birth), respectively. The expression of Olig1 was determined by Western blot and immunostaining. To observe expression of Olig1 in different neural cell types, a double immunohistochemical staining was performed using antibodies against Olig1 with O4, β-tubulin, glial fibrillary acidic protein (GFAP), and myelin basic protein, respectively...
2016: Neuropsychiatric Disease and Treatment
Jialei Yang, Xunyuan Liu, Xiufen Zhang, Xianghui Zhao, Yuanhang Pan, Mengsheng Qiu, Shengxi Wu, Gang Zhao, Ya-Zhou Wang
Proper neuron-glia ratio is essential for normal brain development and function. Olig1 is a basic helix-loop-helix (bHLH) transcription factor generally used as a lineage tool for oligodendrocyte research in spinal cord. Recent studies have revealed a property of Olig1-positive cells as the common progenitors of GABAergic neurons and oligodendrocytes in the forebrain during embryogenesis, and a stage-dependent regulatory role of Wnt/β-catenin signaling in the differentiation of oligodendrocytes in spinal cord...
May 27, 2016: Neuroscience Letters
Heba R Ghaiad, Mohammed M Nooh, Maha M El-Sawalhi, Amira A Shaheen
Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice...
April 11, 2016: Molecular Neurobiology
Peter Falkai, Johann Steiner, Berend Malchow, Jawid Shariati, Andreas Knaus, Hans-Gert Bernstein, Thomas Schneider-Axmann, Theo Kraus, Alkomiet Hasan, Bernhard Bogerts, Andrea Schmitt
In schizophrenia, previous stereological post-mortem investigations of anterior, posterior, and total hippocampal subfields showed no alterations in total neuron number but did show decreased oligodendrocyte numbers in CA4, an area that corresponds to the polymorph layer of the dentate gyrus (DG). However, these investigations identified oligodendrocytes only on the basis of morphological criteria in Nissl staining and did not assess alterations of interneurons with immunohistochemical markers. Moreover, the association of findings in the posterior hippocampus with cognitive deficits remains unknown...
2016: Frontiers in Cellular Neuroscience
Tao Yang, Qi Zheng, Hui Zhao, Qiu-Xia Zhang, Ming Li, Fang Qi, Kang-Ning Li, Ling Fang, Lei Wang, Yong-Ping Fan
OBJECTIVE: To study the effects of Bushen Yisui Capsule (, BSYSC) on the oligodendrocyte lineage genes (Olig) 1 and Olig2 in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE) in order to explore the remyelination effect of BSYSC. METHODS: The mice were randomly divided into normal control (NC), EAE model (EAE-M), prednisone acetate (PA, 6 mg/kg), BSYSC high-dose (3.02 g/kg) and BSYSC low-dose (1.51 g/kg) groups. The mice were induced by immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55...
December 2016: Chinese Journal of Integrative Medicine
Di Xie, Fengcai Shen, Shaoru He, Mengmeng Chen, Qianpeng Han, Ming Fang, Hongke Zeng, Chunbo Chen, Yiyu Deng
Neuroinflammation elicited by microglia plays a key role in periventricular white matter (PWM) damage (PWMD) induced by infectious exposure. This study aimed to determine if microglia-derived interleukin-1β (IL-1β) would induce hypomyelination through suppression of maturation of oligodendrocyte progenitor cells (OPCs) in the developing PWM. Sprague-Dawley rats (1-day old) were injected with lipopolysaccharide (LPS) (1 mg/kg) intraperitoneally, following which upregulated expression of IL-1β and IL-1 receptor 1 (IL-1R1 ) was observed...
April 2016: Glia
Jinxiang Dai, Kathryn K Bercury, Weilin Jin, Wendy B Macklin
The oligodendrocyte transcription factor Olig1 is critical for both oligodendrocyte development and remyelination in mice. Nuclear to cytoplasmic translocation of Olig1 protein occurs during brain development and in multiple sclerosis, but the detailed molecular mechanism of this translocation remains elusive. Here, we report that Olig1 acetylation and deacetylation drive its active translocation between the nucleus and the cytoplasm in both mouse and rat oligodendrocytes. We identified three functional nuclear export sequences (NES) localized in the basic helix-loop-helix domain and one specific acetylation site at Lys 150 (human Olig1) in NES1...
December 2, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jenna J Boulanger, William A Staines, Véronique LeBlanc, Eve-Ling Khoo, Jacky Liang, Claude Messier
The typical immunohistochemistry technique used to reveal 5-bromo-2'-deoxyuridine (BrdU) incorporation requires denaturation of the DNA by heat and acid to permeabilize the cell nucleus. This treatment can damage tissue and reduce the antigenicity of several proteins, which then leads to weak immunostaining and/or false negatives. We show that an overnight post-fixation step following immunohistochemistry for antigens of interest protects immunostaining during the acid/heat denaturation treatment for subsequent BrdU staining...
February 1, 2016: Journal of Neuroscience Methods
Andrew M Ravanelli, Bruce Appel
During spinal cord development, ventral neural progenitor cells that express the transcription factors Olig1 and Olig2, called pMN progenitors, produce motor neurons and then oligodendrocytes. Whether motor neurons and oligodendrocytes arise from common or distinct progenitors in vivo is not known. Using zebrafish, we found that motor neurons and oligodendrocytes are produced sequentially by distinct progenitors that have distinct origins. When olig2(+) cells were tracked during the peak period of motor neuron formation, most differentiated as motor neurons without further cell division...
December 1, 2015: Genes & Development
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