Therapeutic Effects of Low-Intensity Treadmill Exercise on Motor and Non-Motor Symptoms in a 6-Hydroxydopamine (OHDA) Rat Model of Parkinson's Disease via Gut-Brain Axis Modulation.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms that substantially reduce quality of life. Current pharmacological treatments primarily target motor deficits and often fail to address non-motor symptoms, underscoring the need for adjunctive strategies. The study aimed to evaluate the therapeutic potential of low-intensity treadmill exercise initiated shortly after the induction of PD using 6-hydroxydopamine (6-OHDA) in rats, with particular emphasis on its modulatory effects on both motor and non-motor symptoms through gut-brain axis regulation. A 10-week low-intensity treadmill exercise regimen (15 or 30 min per day) was administered to 6-OHDA-lesioned rats, followed by assessments including rotarod testing, Morris water maze performance, tyrosine hydroxylase (TH) immunostaining, cytokine profiling, and gut microbiota analysis. The results found that low-intensity treadmill exercise significantly improved motor coordination and cognitive performance, as evidenced by enhanced rotarod test scores and reduced escape latency in the Morris water maze, alongside partial preservation of dopaminergic neurons in the striatum and substantia nigra pars compacta as revealed by TH immunostaining. In addition, low-intensity treadmill exercise promoted gastrointestinal improvements, including enhanced motility, increased expression of zonula occludens-1 (ZO-1), and beneficial alterations in gut microbiota composition. Moreover, exercise reduced proinflammatory cytokines in the serum, striatum, and colon, while increasing anti-inflammatory IL-10 levels in the serum. These findings suggest that low-intensity treadmill exercise alleviates both motor and non-motor manifestations of PD by modulating the gut-brain axis, providing mechanistic insight into an established, non-pharmacological strategy for disease management.