Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
J Mol Neurosci. 2018 Apr;64(4):591-600. doi: 10.1007/s12031-018-1061-y. Epub 2018 Apr 5.
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.
少突胶质前体细胞（OPCs）的增殖和分化对于白质损伤后的髓鞘修复至关重要。星形胶质细胞在白质损伤后可以促进少突胶质细胞发生，但其潜在机制尚不清楚。在本研究中，评估了星形胶质细胞缝隙连接蛋白 43（Cx43）半通道在慢性缺氧条件下对 OPC 增殖和分化的作用。在星形胶质细胞-OPC 共培养的慢性缺氧模型中，OPC 变得增殖，但未能成熟为少突胶质细胞。星形胶质细胞 Cx43 阻断剂的应用减弱了星形胶质细胞的激活，抑制了缺氧诱导的 Cx43 半通道摄取活性和谷氨酸释放，并改善了 OPC 分化。此外，AMPA 而不是 NMDA 谷氨酸受体拮抗剂可挽救缺氧诱导的 OPC 分化。总之，这些发现表明，星形胶质细胞 Cx43 半通道抑制可通过减弱 AMPAR 介导的谷氨酸信号来改善 OPC 的成熟。星形胶质细胞 Cx43 半通道可能成为慢性缺氧后髓鞘修复的潜在治疗靶点。
