维持小胶质细胞稳态需要NG2胶质细胞  

NG2 glia are required for maintaining microglia homeostatic state

作　　者：Yingjun Liu Adriano Aguzzi 杜一星(编译) Yingjun Liu;Adriano Aguzzi(Institute of Neuropathology,University of Zurich,Zurich,Switzerland.)

机构地区：[1]Institute of Neuropathology,University of Zurich,Zurich,Switzerland [2]不详

出　　处：《神经损伤与功能重建》2021年第1期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：小胶质细胞在中枢神经系统的健康和疾病状态中起着至关重要的作用。小胶质细胞稳态的丧失是脑衰老和神经变性的关键特征。然而,维持小胶质细胞独特细胞状态的机制尚不清楚。本研究显示NG2胶质细胞,也称为少突胶质细胞前体细胞,对于维持小胶质细胞稳态至关重要。我们开发了一种高效的、选择性的NG2胶质细胞耗竭方法,该方法在培养的脑切片中使用血小板衍生的生长因子(PDGF)信号通路的小分子抑制剂。我们发现,NG2胶质细胞的丧失消除了稳态的小胶质细胞特征,而并不影响与疾病相关的小胶质细胞特征。通过遗传消耗NG2胶质细胞或条件性地抑制NG2胶质细胞PDGF信号,我们在成年小鼠脑中也在体观察到了类似的发现。这些数据表明,NG2胶质细胞对与脑衰老和神经退行性疾病相关的小胶质细胞状态起着至关重要的作用。此外,本研究结果为研究NG2胶质细胞功能提供了一个强大、便捷且具选择性的研究手段。Microglia play vital roles in the health and diseases of the central nervous system.Loss of microglia homeostatic state is a key feature of brain aging and neurodegeneration.However,the mechanisms underlying the maintenance of distinct microglia cellular states are largely unclear.Here,we show that NG2 glia,also known as oligodendrocyte precursor cells,are essential for maintaining the homeostatic microglia state.We developed a highly efficient and selective NG2 glia depletion method using small-molecule inhibitors of platelet-derived growth factor(PDGF)signaling in cultured brain slices.We found that loss of NG2 glia abolished the homeostatic microglia signature without affecting the disease-associated microglia profiles.Similar findings were also observed in vivo by genetically depleting NG2 glia or conditionally inhibiting NG2 glia PDGF signaling in the adult mouse brain.These data suggest that NG2 glia exert a crucial influence onto microglia cellular states that are relevant to brain aging and neurodegenerative diseases.In addition,our results provide a powerful,convenient,and selective tool for the investigation of NG2 glia function.

关 键 词：小胶质细胞稳态 神经退行性疾病 少突胶质细胞前体细胞 器官型培养脑组织片 血小板衍生生长因子 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]