Resveratrol Improves Fine Motor Performance and Attenuates Oxidative Stress, GFAP Reactivity, and Purkinje Cell Loss in the Cerebellum of Male Rats After 12, 18, and 24 Months of Treatment

The cerebellum contributes to motor, cognitive, and affective functions that progressively decline with aging. The search for effective therapies to delay age-related degeneration has become a focus of the scientific community. Resveratrol, a natural polyphenol, exhibits neuroprotective properties through antioxidant and anti-inflammatory actions in different models of brain injury and aging. Here, we evaluated the effects of resveratrol on fine motor performance, oxidative stress, glial reactivity, and Purkinje cell survival in the cerebellum of male Wistar rats treated for 6, 12, 18, or 24 months. Three-month-old rats were randomly assigned to receive either vehicle (drinking water) or resveratrol (10 mg/kg, orally, daily by gavage between 8:00 and 10:00 a.m.). Fine motor skills were assessed using the balance beam test. Rats treated with resveratrol for 18 or 24 months showed improved motor coordination and fewer slips compared with controls. Histological analysis revealed less cellular disorganization and greater preservation of Purkinje cells after 12, 18, and 24 months of treatment. Nissl staining confirmed that resveratrol attenuated neuronal disintegration and preserved cerebellar architecture. Moreover, resveratrol significantly reduced GFAP immunoreactivity at 12, 18, and 24 months, indicating decreased astrocytic activation and inflammation. In conclusion, chronic resveratrol treatment exerted neuroprotective effects in the cerebellum, improving fine motor performance and reducing glial reactivity. These findings support resveratrol as a potential strategy to mitigate motor decline, inflammation, and cerebellar neurodegeneration associated with aging.