Xu Miao-Miao, Hu Dan-Ting, Zhang Qiao, Liu Xiao-Guang, Li Zhao-Wei, Lu Li-Ming
School of Sports and Health, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Sheng Li Xue Bao. 2025 Jun 25;77(3):419-431. doi: 10.13294/j.aps.2025.0049.
Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopaminergic neurons in the midbrain substantia nigra. This study aimed to investigate the effects of exercise preconditioning on motor deficits and mitochondrial function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sedentary + saline (SS), sedentary + MPTP (SM), exercise + saline (ES), and exercise + MPTP (EM) groups. Mice in the ES and EM groups received 4 weeks of treadmill training, and then SM and EM groups were treated with MPTP for 5 days. Motor function was assessed by behavioral tests, and morphological and functional changes in dopaminergic neurons and mitochondria in the substantia nigra of the midbrain were evaluated using immunohistochemistry, Western blot, and transmission electron microscopy technology. The results showed that, compared with the SM group, the EM group exhibited significantly improved motor ability, up-regulated protein expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the midbrain, and down-regulated protein expression of α-synuclein (α-Syn) in the mitochondria of substantia nigra. Compared with the SM group, the EM group showed up-regulated protein expression levels of mitochondrial fusion proteins, including optical atrophy protein 1 (OPA1) and mitofusin 2 (MFN2), and biogenesis-related proteins, including peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), while the protein expression levels of dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1) were significantly down-regulated. Compared with the SM group, the EM group showed significantly reduced damage to substantia nigra mitochondria, restored mitochondrial membrane potential and ATP production, and decreased levels of reactive oxygen species (ROS). These results suggest that 4-week treadmill pre-training can alleviate MPTP-induced motor impairments in PD mice by improving mitochondrial function, providing a theoretical basis for early exercise-based prevention of PD.
帕金森病（PD）是一种常见的神经退行性疾病，主要与中脑黑质多巴胺能神经元的线粒体功能障碍有关。本研究旨在探讨运动预处理对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠模型运动功能障碍和线粒体功能的影响。将8周龄雄性C57BL/6J小鼠随机分为四组：静息+生理盐水（SS）组、静息+MPTP（SM）组、运动+生理盐水（ES）组和运动+MPTP（EM）组。ES组和EM组小鼠接受4周的跑步机训练，然后SM组和EM组用MPTP处理5天。通过行为测试评估运动功能，使用免疫组织化学、蛋白质印迹和透射电子显微镜技术评估中脑黑质多巴胺能神经元和线粒体的形态和功能变化。结果显示，与SM组相比，EM组运动能力显著改善，中脑酪氨酸羟化酶（TH）和多巴胺转运体（DAT）蛋白表达水平上调，黑质线粒体中α-突触核蛋白（α-Syn）蛋白表达下调。与SM组相比，EM组线粒体融合蛋白包括视神经萎缩蛋白1（OPA1）和线粒体融合蛋白2（MFN2）以及生物发生相关蛋白包括过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）和线粒体转录因子A（TFAM）的蛋白表达水平上调，而动力相关蛋白1（DRP1）和线粒体分裂蛋白1（FIS1）的蛋白表达水平显著下调。与SM组相比，EM组黑质线粒体损伤显著减轻，线粒体膜电位和ATP生成恢复，活性氧（ROS）水平降低。这些结果表明，4周的跑步机预训练可通过改善线粒体功能减轻MPTP诱导的PD小鼠运动障碍，为基于运动的PD早期预防提供理论依据。
