Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783454214922436608 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6763517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wangqiong inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT wangzhen inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT tianyeye inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT zhanghuaqiu inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT fangyongkang inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT yuzhiyuan inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT wangwei inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT xieminjie inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro AT dingfengfei inhibitionofastrocyteconnexin43channelsfacilitatesthedifferentiationofoligodendrocyteprecursorcellsunderhypoxicconditionsinvitro |