Exercise therapy represents an important tool for the treatment of many neurological diseases, including cerebellar degenerations. In mouse models, exercise may decelerate the progression of gradual cerebellar degeneration via potent activation of neuroprotective pathways. However, whether exercise could also improve the condition in mice with already heavily damaged cerebella remains an open question. Here we aimed to explore this possibility, employing a mouse model with dramatic early-onset cerebellar degeneration, the Lurcher mice. The potential of forced physical activity and environmental enrichment (with the possibility of voluntary running) for improvement of behaviour and neuroplasticity was evaluated by a series of behavioural tests, measuring BDNF levels and using stereological histology techniques. Using advanced statistical analysis, we showed that while forced physical activity improved motor learning by ∼26 % in Lurcher mice and boosted BDNF levels in the diseased cerebellum by 57 %, an enriched environment partially alleviated some behavioural deficits related to behavioural disinhibition. Specifically, Lurcher mice exposed to the enriched environment evinced reduced open arm exploration in elevated plus maze test by 18 % and increased immobility almost 9-fold in the forced swim test. However, we must conclude that the overall beneficial effects were very mild and much less clear, compared to previously demonstrated effects in slowly-progressing cerebellar degenerations.

Department of Pathological Physiology Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic; Laboratory of Neurodegenerative Disorders Biomedical Center Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic

References provided by Crossref.org

Lurcher Mouse as a Model of Cerebellar Syndromes

Experimental Treatment with Edaravone in a Mouse Model of Spinocerebellar Ataxia 1

Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications