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Exercise preconditioning alleviates motor deficits in MPTP-induced Parkinsonian mice by improving mitochondrial function

XU Miao-Miao^1,2, HU Dan-Ting¹, ZHANG Qiao², LIU Xiao-Guang³, LI Zhao-Wei¹, LU Li-Ming^2,*

¹School of Sports and Health, Guangzhou University of Chinese Medicine, Guangzhou 510006, China；²Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China；³School of Exercise and Health, Guangzhou Sport University, Guangzhou 510620, China

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopami nergic 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-weekold 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.

Key words: Parkinson''s disease; treadmill pre-training; mitochondrial function; dopaminergic neurons; mitochondrial dynamics

Received: 　　Accepted:

Corresponding author: 陆丽明　　E-mail:

DOI: 10.13294/j.aps.2025.0049

Citing This Article：

XU Miao-Miao, HU Dan-Ting, ZHANG Qiao, LIU Xiao-Guang, LI Zhao-Wei, LU Li-Ming. Exercise preconditioning alleviates motor deficits in MPTP-induced Parkinsonian mice by improving mitochondrial function. Acta Physiol Sin 2025; 77 (3): 419-431 (in Chinese with English abstract).