Effects of Body-Weight Resistance Exercise on Motor Function and Mitochondrial Quality Control in a Parkinson’s Disease Mouse Model

PURPOSE: Body-weight resistance exercise (BR) has been suggested to improve motor function and confer neuroprotection in Parkinson’s disease (PD); however, the underlying molecular mechanisms remain poorly understood. Given that mitochondrial dysfunction is a hallmark of PD pathology, this study investigated whether BR-induced neuroprotection is associated with mitochondrial quality control in a mouse model of PD induced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).METHODS: Human SH-SY5Y cells were treated with 1 mM MPP+ to assess changes in mitochondrial complex levels and cell viability. For in vivo experiments, C57BL/6 male mice were randomly assigned to three groups: control (CON, n=8), MPTP (MPTP, n=8), and MPTP plus BR (MPTP+BR, n=8). MPTP+BR mice performed progressive body-weight ladder-climbing exercise 5 days per week for 12 weeks.RESULTS: MPP+ treatment significantly reduced mitochondrial complex I–V levels and decreased cell viability. Consistently, MPTP administration impaired motor performance and reduced tyrosine hydroxylase expression in the substantia nigra. BR intervention markedly restored motor function and increased tyrosine hydroxylase levels. Furthermore, BR enhanced mitochondrial fusion proteins (MFN1 and OPA1), modulated fission-related proteins (FIS1 and DRP1), and activated PINK1-mediated mitophagy, while PGC-1α expression remained unchanged.CONCLUSIONS: These findings demonstrate that BR attenuates PD-related motor deficits and dopaminergic neuronal loss by restoring mitochondrial dynamics and selectively activating mitophagy. Our results suggest that BR-induced mitochondrial quality control may represent a promising non-pharmacological therapeutic strategy for the management of PD.