Research ReportNeuroprotective effects of moderate aerobic exercise on the spastic Han-Wistar rat, a model of ataxia

Research has shown that physical exercise may reduce degeneration in certain brain regions experiencing ataxia. Our laboratory utilized mutant spastic Han-Wistar rats (sHW) that display developmental abnormalities, including spastic paresis, fore limb tremors, hind limb rigidity, and a reduced life span (60-65 days of age). Concomitant neurodegeneration has been observed in the cerebellum (Purkinje cells). The purpose of this study was to investigate if moderate, aerobic exercise could reduce Purkinje cell neurodegeneration and improve the motor ability and survival of the mutant sHW rat. Mutant male littermates at the ages of 20 (n = 11 pairs) and 30 (n = 13 pairs) days old were divided into running groups and non-running groups. Mutant rats were run on a motorized treadmill at the rate of 15 m/min with a 10% slope. The “running” group ran for 30 min per day, 5 days a week; the “non-runners” remained nearby in the training facility. These conditions were held constant until the mutant runners could no longer run due to disease progression. Moderate exercise increased the lifespan of running mutant rats in both the 20-day start group (14% increase) and 30-day start group (13% increase). The rats exhibited improved motor function as open-field tests showed higher activity scores for runners after 50 days. Histological examination of the cerebellum revealed a 62% increase in Purkinje cell survival of the runners. These results suggest that aerobic exercise ameliorates, at least partially, cerebellar dysfunction in the sHW rat, an excellent model of ataxia.

Research Highlights► Moderate treadmill exercise significantly extended the survivorship of spastic Han-Wistar rats. ► Results were similar whether exercise started at 20 or 30 days of age. ► Corroborating results were seen in sustained weight gain and motor activity after 50 days of age. ► There was a significant increase in Purkinje cell survival in the cerebellum of exercising mutants.