Cardiovascular exercise drives neuroprotection in Spinocerebellar Ataxia 1 via rescue of abherrant splicing

Exercise remains the only intervention shown to provide clinical benefit in patients with spinocerebellar ataxias, yet the underlying mechanisms remain poorly understood. Results: Unrestricted exercise rescued motor ataxia in SCA1 mice but not degeneration in this model at the ages in this study.

Transcriptional profiling of cerebellar tissue did separate WT sedentary and exercise mice by differential gene expression, but in SCA1 mice the most pronounced changes occurred at the level of RNA splicing, particularly in ion channel modules. Exercise led to a significant rescue of splicing events in SCA1 mice, with minimal impact on gene expression changes. Further, both exercised SCA1 and wild-type mice exhibited splicing patterns more similar to each other than their sedentary counterparts.