Effects of Moderate-Intensity Treadmill Exercise on Motor Function and Striatal Neuronal Activity in a Severe Rat Model of Parkinson’s Disease

Background: The effects of exercise on patients with severe Parkinson’s disease (PD) with marked dopaminergic loss remain unclear. This study examined whether moderate treadmill exercise improves motor function and striatal neuronal activity in a rat model of severe Parkinson’s disease. Methods: Male rats with unilateral medial forebrain bundle lesions were assigned to the exercise (EX) or sedentary (SED) groups. The EX group performed moderate treadmill training five times a week for four weeks. Motor function was assessed using beam-walking tests with DeepLabCut-based gait and posture analyses. Dopaminergic integrity was evaluated using tyrosine hydroxylase (TH) immunostaining, and neuronal activity was assessed using c-Fos immunostaining. Apomorphine-induced rotation was also analyzed. Results: No significant differences were observed in body weight, motor performance, gait parameters, TH-positive areas, or rotational behavior between the groups. However, c-Fos-positive cells in the lesioned striatum were significantly higher in the EX group than in the SED group (p < 0.05), whereas no difference was found in the intact hemisphere. Discussion: Moderate-intensity exercise did not improve motor deficits or dopaminergic loss in this severe model but increased c-Fos expression in the lesioned striatum. These findings suggest that neural responsiveness to exercise is preserved even under advanced dopaminergic degeneration, although longer intervention periods or higher exercise doses may be required to achieve functional recovery.