Objective To observe the effects of voluntary exercise on the learning ability, memory and hippocampus growth-associated protein 43 (GAP43) expression in senescence-accelerated prone mouse (SAMP8), so as to explore the possible mechanism of exercises on improving the cognitive ability and delaying aging. MethodsA total of 60 three-month old female SAMP8 mice were evenly assigned to running cage environment (RCE) group and standard environment (SE) group at random. After three months, Morris water maze test was used to test the platform-seeking latency and search strategy. Then 10 mice were sacrificed in each group for RT-PCR analysis of hippocampus GAP43 mRNA expression, 10 for Western blotting analysis of hippocampus GAP43 protein expression, and 10 for immunohistochemistry staining of hippocampus GAP43 expression. ResultsMorris water maze test showed that RCE mice had a significant shorter platform-seeking latency than SE mice(P<0.01, P<0.05), and RCE mice had a significant longer time in the first quadrant (P<0.01) and a shorter time in the fourth quadrant (P<0.05) compared with SE mice. RCE mice had a significantly higher GAP43 expression in the hippocampus compared with SE mice (P<0.01). ConclusionVoluntary exercise can improve the learning ability and memory of SAMP8, which might be associated with the increase of GAP43 in the hippocampus.