Y39C human mutant α-synuclein transgenic mice performed daily running wheel exercise for three months which led to improved motor and cognitive function.

<p>12-month-old Y39C transgenic mice were divided into Exercise and Non-Exercise groups (n = 7 for each group) following pre-testing of all 14 animals in individual cages with running wheels. Animals were assigned to Exercise and Non-Exercise groups by alternating rank order following their week-long pre-test. Exercise mice had free access to individual cage-mounted running wheels and Non-Exercise mice had a locked, non-functioning running wheel in individual cages. Daily running distances of the Exercise animals were recorded and averaged for each week. (<b>A</b>) Data show that all animals continued running for 12 weeks with some reduction in running speed. Average distance in the first week was 3.76 ± 0.87 miles per day. Average distance in the 12^th week was 2.71 ± 0.53 miles per day (no statistical difference between 1^st and 12^th week, n = 7, multi-variance ANOVA, <i>p</i> = 0.33). After 12-weeks of running wheel activity, all mice were tested for high intensity motor activity on the Rotarod (<b>B</b>) and cognitive function using a Morris water maze (<b>C</b>). (<b>B</b>) In the Rotarod test, the Exercise group could remain on the rod significantly longer at 26 rpm than the Non-Exercise group (n = 7, multi-variance ANOVA, **<i>p =</i> 0.001). (<b>C</b>) In the Morris water maze, the Exercise mice took significantly less time to find the hidden platform at Day 5 than Non-Exercise transgenic mice (n = 7, multi-variance ANOVA, *<i>p =</i> 0.02).