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

  • Qiong Wang
  • Zhen Wang
  • Yeye Tian
  • Huaqiu Zhang
  • Yongkang Fang
  • Zhiyuan Yu
  • Wei Wang
  • Minjie Xie
  • Fengfei Ding
Article
  • 57 Downloads

Abstract

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.

Keywords

Astrocyte Oligodendrocyte precursor cells Oligodendrocyte Connexin43 Glutamate Hypoxia 

Notes

Acknowledgments

The investigation was supported by the National Natural Science Foundation of China (81571113, 61327902), the Program for Changjiang Scholars and Innovative Research Team in University (IRT_14R20), and grant from the Fundamental Research Funds for the Central Universities (2017KFYXJJ097), the Huazhong University of Science and Technology “Double Top” Construction Pro-ject of International Cooperation (grant 540-5001540013). Acknowledgements to Jia Li, Li Xu, and Xiaojiang Huang in contribution in preliminary data collections.

Supplementary material

12031_2018_1061_MOESM1_ESM.doc (366 kb)
ESM 1 (DOC 365 kb)

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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.

Authors and Affiliations

  1. 1.Department of Neurology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Department of Neurosurgery, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  3. 3.Key Laboratory of Neurological Diseases of Chinese Ministry of Education, the School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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