Aim: Parkinson’s disease is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and motor symptoms. It is associated with mitochondrial dysfunction and reduced expression of key mitochondrial biogenesis genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial transcription factor A (TFAM), and cytochrome c oxidase (COX). Considering the potential of exercise to improve mitochondrial function, this study aimed to investigate the effects of aerobic, resistance, and combined training on the expression of these genes in a rat model of Parkinson’s disease.

Methods: In this randomized controlled experimental study, fifty male Wistar rats (8 weeks, 250 ± 50 g) were randomly assigned to five groups (n=10). Parkinsonism was induced by unilateral intrastriatal 6-OHDA injection. Exercise protocols included treadmill running (30 to 60 min, 10 to 15 m/min), ladder climbing (5 to 15% body weight), and combined training (3 aerobic + 2 resistance sessions/week) for 8 weeks. Twenty-four hours after the final session, substantia nigra and striatum were collected for qPCR of PGC-1α, TFAM, and COX. Data were analyzed using two-way ANOVA with Bonferroni post-hoc (SPSS v.26, p<0.05).

Results: All exercise interventions significantly increased the expression of all three genes compared to the Parkinsonian sedentary group (p≤0.05). However, combined training had the superior effect, significantly surpassing both aerobic exercise (for PGC-1α: p=0.04; TFAM: p=0.03; COX: p=0.05) and resistance training (for PGC-1α: p=0.02; TFAM: p=0.01; COX: p=0.02). Aerobic training also produced notable positive effects, while improvements from resistance training were smaller.

Conclusion: Exercise training, particularly the combination of aerobic and resistance modalities, is an effective strategy to enhance mitochondrial biogenesis markers in the Parkinsonian brain. This molecular adaptation acts as a neuroprotective mechanism and provides strong scientific justification for the clinical application of structured exercise as a non-pharmacological intervention in the management of Parkinson’s disease