Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Key Laboratory of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, China.
Department of Rehabilitation Medicine, University - Town Hospital, Chongqing Medical University, Chongqing, 401331, China.
Brain Res Bull. 2021 Mar;168:52-62. doi: 10.1016/j.brainresbull.2020.12.010. Epub 2020 Dec 29.
Recent studies have discovered a strong link between physical exercise and the prevention of neuro-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 up-regulation of ROCK signal pathway.
最近的研究发现,体育锻炼与神经退行性症状的预防之间存在很强的关联,特别是在老年人群体中。然而,确切的潜在机制尚不清楚。在这项研究中,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的髓鞘有保护作用,该信号通路被认为是减少细胞凋亡和促进神经再生的关键机制。简要地说,C57/BL 老年小鼠进行了运动训练(每周 5 天,持续 6 周)。使用新物体识别(NOR)测试和 Morris 水迷宫测试(MWM)来检测记忆和认知障碍。在胼胝体(CC)中使用卢索快速蓝染色和透射电子显微镜来探索脱髓鞘,通过 Western blot 分析 ROCK 和凋亡蛋白的表达。我们证明了老年小鼠的记忆和认知损伤以及髓鞘厚度的减少。此外,在老年小鼠中观察到严重的脱髓鞘,伴随着 RhoA、ROCK、ATF3 和 Caspase 3 的表达增加,以及 MBP、Olig2 和 NG2 的表达减少。有氧运动训练改善了行为功能,增加了 MBP 的表达和髓鞘厚度,减少了细胞凋亡并促进了髓鞘形成。总之,我们的数据表明,有氧运动训练可防止与年龄相关的白质损伤引起的脱髓鞘,这与 ROCK 信号通路的上调有关。