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Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro

Oligodendrocyte precursor cells (OPCs) proliferation and differentiation are essential for remyelination after white matter injury. Astrocytes could promote oligodendrogenesis after white matter damage whereas the underlying mechanisms are unknown. In this study, the role of astrocytic connexin43 (C...

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Autores principales: Wang, Qiong, Wang, Zhen, Tian, Yeye, Zhang, Huaqiu, Fang, Yongkang, Yu, Zhiyuan, Wang, Wei, Xie, Minjie, Ding, Fengfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763517/
https://www.ncbi.nlm.nih.gov/pubmed/29623602
http://dx.doi.org/10.1007/s12031-018-1061-y
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author Wang, Qiong
Wang, Zhen
Tian, Yeye
Zhang, Huaqiu
Fang, Yongkang
Yu, Zhiyuan
Wang, Wei
Xie, Minjie
Ding, Fengfei
author_facet Wang, Qiong
Wang, Zhen
Tian, Yeye
Zhang, Huaqiu
Fang, Yongkang
Yu, Zhiyuan
Wang, Wei
Xie, Minjie
Ding, Fengfei
author_sort Wang, Qiong
collection PubMed
description Oligodendrocyte precursor cells (OPCs) proliferation and differentiation are essential for remyelination after white matter injury. Astrocytes could promote oligodendrogenesis after white matter damage whereas the underlying mechanisms are unknown. In this study, the role of astrocytic connexin43 (Cx43) hemichannels involved in OPC proliferation and differentiation in chronic hypoxia was evaluated. In an astrocyte-OPC co-culture chronic hypoxia model, OPCs became proliferative but failed to mature into oligodendrocytes. Application of astrocytic Cx43 blockers attenuated astrocyte activation, suppressed Cx43 hemichannel uptake activity and glutamate release induced by hypoxia, as well as improved OPC differentiation. Moreover, AMPA but not NMDA glutamate receptor antagonist rescued OPC differentiation in hypoxia. In conclusion, these findings suggested that astrocytic Cx43 hemichannel inhibition could potentially improve OPC maturation by attenuating AMPAR-mediated glutamate signaling. Astrocytic Cx43 hemichannels could serve as a potential therapeutic target for remyelination after chronic hypoxia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12031-018-1061-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-67635172019-10-07 Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro Wang, Qiong Wang, Zhen Tian, Yeye Zhang, Huaqiu Fang, Yongkang Yu, Zhiyuan Wang, Wei Xie, Minjie Ding, Fengfei J Mol Neurosci Article Oligodendrocyte precursor cells (OPCs) proliferation and differentiation are essential for remyelination after white matter injury. Astrocytes could promote oligodendrogenesis after white matter damage whereas the underlying mechanisms are unknown. In this study, the role of astrocytic connexin43 (Cx43) hemichannels involved in OPC proliferation and differentiation in chronic hypoxia was evaluated. In an astrocyte-OPC co-culture chronic hypoxia model, OPCs became proliferative but failed to mature into oligodendrocytes. Application of astrocytic Cx43 blockers attenuated astrocyte activation, suppressed Cx43 hemichannel uptake activity and glutamate release induced by hypoxia, as well as improved OPC differentiation. Moreover, AMPA but not NMDA glutamate receptor antagonist rescued OPC differentiation in hypoxia. In conclusion, these findings suggested that astrocytic Cx43 hemichannel inhibition could potentially improve OPC maturation by attenuating AMPAR-mediated glutamate signaling. Astrocytic Cx43 hemichannels could serve as a potential therapeutic target for remyelination after chronic hypoxia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12031-018-1061-y) contains supplementary material, which is available to authorized users. Springer US 2018-04-05 2018 /pmc/articles/PMC6763517/ /pubmed/29623602 http://dx.doi.org/10.1007/s12031-018-1061-y Text en © Springer Science+Business Media, LLC, part of Springer Nature 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Wang, Qiong
Wang, Zhen
Tian, Yeye
Zhang, Huaqiu
Fang, Yongkang
Yu, Zhiyuan
Wang, Wei
Xie, Minjie
Ding, Fengfei
Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
title Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
title_full Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
title_fullStr Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
title_full_unstemmed Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
title_short Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
title_sort inhibition of astrocyte connexin 43 channels facilitates the differentiation of oligodendrocyte precursor cells under hypoxic conditions in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763517/
https://www.ncbi.nlm.nih.gov/pubmed/29623602
http://dx.doi.org/10.1007/s12031-018-1061-y
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