Molecular Mechanisms of the Effects of Aerobic Exercise on Cerebellar Brain-Derived Neurotrophic Factor

Abstract

Context: Aerobic exercise (AE) is a nonpharmacological strategy that may support nervous system function. AE increases the expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the circulation and several brain regions. BDNF is highly expressed in the hippocampus and cerebellum and is among the most extensively studied neurotrophins in relation to physical activity. Given the importance of AE in maintaining and promoting cerebellar function, this review evaluated the effects of AE on cerebellar BDNF and the molecular mechanisms that may underlie these effects. Evidence Acquisition: This narrative review searched PubMed for studies examining the effects of AE on BDNF and cerebellar neurogenesis. The literature search was conducted between November and December 2024 and included publications from 2000 to 2024. Results: Based on the inclusion and exclusion criteria, 19 PubMed articles examining the effects of AE on BDNF expression were identified. These studies were published between 2002 and 2022; no eligible articles were identified in 2000, 2001, 2023, or 2024. Thirteen studies used rats, 5 used mice, and 1 involved BALB/c mice. Eight studies investigated treadmill running, 7 used wheel running, 2 used swimming training, 1 used gait training, and 1 examined running on a flat track. Overall, 3 studies reported no significant effect of AE on BDNF expression in cerebellar tissue, whereas the remaining 16 studies reported increased BDNF expression and improved cerebellar function in healthy rodents and in models of menopause, lactation, depression, ataxia, early-onset cerebellar degeneration, and spinocerebellar ataxia type 6. Conclusions: Based on the available evidence, AE may represent a promising strategy for improving cerebellar function, potentially by increasing BDNF expression and activity.