Zhang Qing, Xu Yangjie, Luo Haodong, Su Hong, Zhong Juan, Pan Lu, Liu Yuan, Yang Ce, Yin Ying, Tan Botao
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Chongqing, 400000, China.
Guangzhou Women and Children'S Medical Center, Guangzhou Medical University, Guangzhou, 510620, China.
Neurochem Res. 2025 Mar 1;50(2):109. doi: 10.1007/s11064-025-04359-1.
Acute and chronic exposure to high altitude causes multiple negative neurological consequences. Further research has shown the efficacy of targeted drugs after acute hypoxia. However, the effects and mechanisms of physical therapy like exercise, on after exposed-induced myelin repair and functional improvements have remained unclear. Here, we explored the efficacy of treadmill training at different intensities on recovery in a rat model of acute hypobaric hypoxia (HH) injury. A 4-week treadmill training scheme was used at 30%, 50%, and 70% of maximum speed. The evolution of oligodendrocyte morphometry was observed by immunofluorescence, and the expressions of myelin-related proteins were detected by western blotting. Transmission electron microscopy (TEM) is used to study fine myelin structure. In addition, the open field test (OFT), elevated plus maze (EPM) and Morris water maze (MWM) were used for the observation of cognitive function recovery. Our study revealed varying degrees of demyelination changes in the cortex and hippocampus following acute hypoxia exposure. Additionally, high-intensity treadmill training enhances oligodendrocyte (OL) maturation, improves myelin-related proteins, and increases myelin sheath thickness, thus facilitating myelin repair, rescuing cognitive function and mood disorders, and preserving normal nerve conduction. Finally, the upregulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) and key enzymes of cholesterol synthesis (HMGCR/FDPS) induced by high-intensity treadmill training was detected. Our results demonstrate that high-intensity treadmill training as a physical therapy via PGC1α and cholesterol synthesis enhances myelin repair and functional restoration, which should provide new insight for the rehabilitation of remyelination by exercise.
急性和慢性暴露于高海拔会导致多种负面的神经学后果。进一步的研究表明了急性缺氧后靶向药物的疗效。然而，运动等物理治疗对暴露后诱导的髓鞘修复和功能改善的影响及机制仍不清楚。在此，我们在急性低压缺氧（HH）损伤大鼠模型中探究了不同强度的跑步机训练对恢复的疗效。采用了一种为期4周的跑步机训练方案，速度为最大速度的30%、50%和70%。通过免疫荧光观察少突胶质细胞形态计量学的演变，通过蛋白质印迹法检测髓鞘相关蛋白的表达。使用透射电子显微镜（TEM）研究精细的髓鞘结构。此外，采用旷场试验（OFT）、高架十字迷宫（EPM）和莫里斯水迷宫（MWM）观察认知功能恢复情况。我们的研究揭示了急性缺氧暴露后皮质和海马体中不同程度的脱髓鞘变化。此外，高强度跑步机训练可促进少突胶质细胞（OL）成熟，改善髓鞘相关蛋白，并增加髓鞘厚度，从而促进髓鞘修复，挽救认知功能和情绪障碍，并维持正常神经传导。最后，检测到高强度跑步机训练诱导的过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1α）和胆固醇合成关键酶（HMGCR/FDPS）的上调。我们的结果表明，高强度跑步机训练作为一种通过PGC1α和胆固醇合成的物理治疗方法，可增强髓鞘修复和功能恢复，这应为运动促进髓鞘再生的康复提供新的见解。
