Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice.
Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice.
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DOI：
10.1007/s12264-021-00745-1
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发表时间：
2021-10
影响因子：
5.6
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Chen L;Ren SY;Li RX;Liu K;Chen JF;Yang YJ;Deng YB;Wang HZ;Xiao L;Mei F;Wang F
暴露在慢性低氧环境中被认为是成年人大脑功能缺陷的危险因素，但其潜在机制在很大程度上仍不清楚。由于活跃的髓鞘生成持续存在于成年中枢神经系统，本研究旨在探讨慢性低氧对成年小鼠髓鞘形成的影响及其相关的功能后果。使用转基因方法标记新生成的髓鞘(NG2-CreERTM；Tau-mGFP)，我们发现髓鞘生成在大多数大脑区域都非常活跃，如运动皮质和胼胝体。低氧(10%氧气)每天12h，连续4周后，4个月龄小鼠脑内髓鞘生成明显受到抑制，光束行走试验显示小鼠运动协调障碍。为了确定髓鞘抑制与功能损伤之间的关系，我们用他莫昔芬(NG2-CreERTM；Tau-mGFP；Olob2 fl/fl)诱导成年小鼠少突胶质细胞特异性的转录因子Orig2的缺失，以模拟缺氧引起的髓鞘生成减少。寡核苷酸缺失抑制了髓鞘生成，从而损害了运动协调性，这表明成年小鼠的运动功能需要髓鞘生成。为了了解增强髓鞘形成是否可以保护脑功能免受缺氧的影响，我们用髓鞘形成增强药物氯马斯汀治疗低氧小鼠，结果是增强了髓鞘形成和改善了运动协调。综上所述，我们的数据表明，慢性低氧抑制髓鞘生成并导致大脑功能缺陷，增强髓鞘生成保护大脑功能免受缺氧相关缺陷的影响。
Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreERTM; Tau-mGFP), we found that myelinogenesis was highly active in most brain regions, such as the motor cortex and corpus callosum. After exposure to hypoxia (10% oxygen) 12 h per day for 4 weeks, myelinogenesis was largely inhibited in the 4-month old brain and the mice displayed motor coordination deficits revealed by the beam-walking test. To determine the relationship between the inhibited myelination and functional impairment, we induced oligodendroglia-specific deletion of the transcription factor Olig2 by tamoxifen (NG2-CreERTM; Tau-mGFP; Olig2 fl/fl) in adult mice to mimic the decreased myelinogenesis caused by hypoxia. The deletion of Olig2 inhibited myelinogenesis and consequently impaired motor coordination, suggesting that myelinogenesis is required for motor function in adult mice. To understand whether enhancing myelination could protect brain functions against hypoxia, we treated hypoxic mice with the myelination-enhancing drug-clemastine, which resulted in enhanced myelogenesis and improved motor coordination. Taken together, our data indicate that chronic hypoxia inhibits myelinogenesis and causes functional deficits in the brain and that enhancing myelinogenesis protects brain functions against hypoxia-related deficits.
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影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
3.8
作者：
Back SA
通讯作者：
Back SA
影响因子：
3.3
作者：
Fan, Junming;Guang, Hui;Gong, Yongsheng
通讯作者：
Gong, Yongsheng
影响因子：
5.3
作者：
Khuu, Maggie A.;Pagan, Chelsea M.;Garcia, Alfredo J., III
通讯作者：
Garcia, Alfredo J., III