Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice
Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice
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DOI：
10.1016/j.brainresbull.2020.12.010
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发表时间：
2021-03-01
影响因子：
3.8
通讯作者：
Li, Hongli
中科院分区：
文献类型：
--
作者：
Bao, Chuncha;He, Chengqi;Li, Hongli
最近的研究发现，体育锻炼与预防神经退行性症状之间有着密切的联系，尤其是在老年人身上，然而，确切的潜在机制尚不清楚。在本研究中，我们假设有氧运动训练可能通过调节ROCK信号通路对老年小鼠髓鞘具有保护作用，而ROCK信号通路被认为是减少细胞凋亡和促进再生的重要机制。简单地说，C57/BL老龄小鼠接受运动训练（每周5天，持续6周）。采用新目标识别（NOR）测试和Morris水迷宫测试（MWM）检测记忆和认知功能障碍。采用Luxol快速蓝染色和透射电镜观察胼胝体（CC）脱髓鞘的变化，western blot检测ROCK和凋亡蛋白的表达。我们证明了老年小鼠的记忆和认知功能障碍以及髓鞘厚度的减少。此外，老龄小鼠严重脱髓鞘，RhoA、ROCK、ATF3、Caspase 3表达升高，MBP、Olig2、NG2表达降低。有氧运动训练可改善行为功能，增加MBP表达和髓鞘厚度，减少细胞凋亡，促进髓鞘形成。综上所述，我们的数据表明，有氧运动训练可以保护脱髓鞘免受衰老相关白质损伤，这与ROCK信号通路上调有关。
Recent studies have discovered a strong link between physical exercise and the prevention of neum-degenerative symptoms, especially in elderly subjects, nonetheless, the exact underlying mechanism remains unclear. In this study, we hypothesized that aerobic exercise training may have a protective effect on myelin sheath in aged mice by regulating the ROCK signal pathway, which is considered as a crucial mechanism for decreasing apoptosis and promoting regeneration. Briefly, C57/BL aged mice underwent an exercise training (5 days/week, lasting 6 weeks). Memory and cognitive impairment were examined using Novel object recognition (NOR) test and Morris water maze test (MWM). Demyelination was explored using Luxol fast blue staining and transmission electron microscopy in the corpus callosum (CC), and the expression of ROCK and apoptotic protein were analyzed via western blot. We demonstrated the impairment of memory and cognitive and the decrease of myelin sheath thickness in aged mice. In addition, severe demyelination was observed in aged mice, accompanied with increased expression of RhoA, ROCK, ATF3, and Caspase 3, and reduced expression of MBP, Olig2, and NG2. Aerobic exercise training improved behavioral functions, increased the expression of MBP and myelin sheath thickness, reduced apoptosis and promoted myelination. To sum up, our data indicate that aerobic exercise training protects demyelination from aging-related white matter injury, which is associated with the upregulation of ROCK signal pathway.