Inhibition of Astrocyte Connexin 43 Channels Facilitates the Differentiation of Oligodendrocyte Precursor Cells Under Hypoxic Conditions In Vitro
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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.
KeywordsAstrocyte Oligodendrocyte precursor cells Oligodendrocyte Connexin43 Glutamate Hypoxia
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.
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