Inhibition of GPR17/ID2 Axis Improve Remyelination and Cognitive Recovery after SAH by Mediating OPC Differentiation in Rat Model

作者全名："Wang, Yingwen; Jiang, Anan; Yan, Jin; Wen, Daochen; Gu, Nina; Li, Zhao; Sun, Xiaochuan; Wu, Yue; Guo, Zongduo"

作者地址："[Wang, Yingwen; Yan, Jin; Gu, Nina; Li, Zhao; Sun, Xiaochuan; Wu, Yue; Guo, Zongduo] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, 1 Youyi Rd, Chongqing, Peoples R China; [Jiang, Anan] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China; [Wen, Daochen] Xuanhan Cty Peoples Hosp, Dept Neurosurg, Dazhou, Peoples R China"

通信作者："Wu, Y; Guo, ZD (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, 1 Youyi Rd, Chongqing, Peoples R China."

来源：TRANSLATIONAL STROKE RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001096174000001

JCR分区：Q1

影响因子：3.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Subarachnoid hemorrhage; GPR17; ID2; Oligodendrocyte; Remyelination

摘要："Myelin sheath injury contributes to cognitive deficits following subarachnoid hemorrhage (SAH). G protein-coupled receptor 17 (GPR17), a membrane receptor, negatively regulates oligodendrocyte precursor cell (OPC) differentiation in both developmental and pathological contexts. Nonetheless, GPR17's role in modulating OPC differentiation, facilitating remyelination post SAH, and its interaction with downstream molecules remain elusive. In a rat SAH model induced by arterial puncture, OPCs expressing GPR17 proliferated prominently by day 14 post-onset, coinciding with compromised myelin sheath integrity and cognitive deficits. Selective Gpr17 knockdown in oligodendrocytes (OLs) via adeno-associated virus (AAV) administration revealed that reduced GPR17 levels promoted OPC differentiation, restored myelin sheath integrity, and improved cognitive deficits by day 14 post-SAH. Moreover, GPR17 knockdown attenuated the elevated expression of the inhibitor of DNA binding 2 (ID2) post-SAH, suggesting a GPR17-ID2 regulatory axis. Bi-directional modulation of ID2 expression in OLs using AAV unveiled that elevated ID2 counteracted the restorative effects of GPR17 knockdown. This resulted in hindered differentiation, exacerbated myelin sheath impairment, and worsened cognitive deficits. These findings highlight the pivotal roles of GPR17 and ID2 in governing OPC differentiation and axonal remyelination post-SAH. This study positions GPR17 as a potential therapeutic target for SAH intervention. The interplay between GPR17 and ID2 introduces a novel avenue for ameliorating cognitive deficits post-SAH."

基金机构："The authors acknowledge the financial support provided by the National Natural Science Foundation of China, Chongqing Science and Health Joint Medical Research Project and the Science and Technology Research Program of Chongqing Municipal Education Commiss; National Natural Science Foundation of China, Chongqing Science and Health Joint Medical Research Project; Science and Technology Research Program of Chongqing Municipal Education Commission"

基金资助正文："The authors acknowledge the financial support provided by the National Natural Science Foundation of China, Chongqing Science and Health Joint Medical Research Project and the Science and Technology Research Program of Chongqing Municipal Education Commission."