Effect of treadmill exercise on spatial learning and memory of autism rats

Abstract

Objective To study the effect of treadmill exercise on spatial learning and memory of autism rats and its possible mechanism. Methods Ten normal wistar rats were chosen as control group, and autism-like animal models were induced in other 20 rats by intraperitoneal injection of 600 mg/kg valproate acid (VPA); the autism models were randomly divided into vehicle group and training group (n=10). The rats in the training group were forced to run on a treadmill for 30 min once a d for 28 consecutive d, while rats in vehicle group and control group were housed on static treadmill only. Then, learning and memory capabilities of all rats were tested by Morris water maze test. Superoxide dismutase (SOD) and catalase (CAT) activities and methylene dioxyamphetamine (MDA) content of the hippocampus tissues were subsequently detected by ELISA Kits. Brain-derived neurotrophic factor (BDNF), phosphorylate (p)-protein kinase (Akt), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) expressions in the hippocampus CA1 were detected by Western blotting. Nissl staining and NeuN immunohistochemistry were utilized to observe the number of normal and mature neurons. Results (1) As compared with rats in the vehicle group, the rats in the training group had significantly shortened escape latency and increased times of passing through the platform (P<0.05). (2) Nissl staining indicated that as compared with the rats in the vehicle group, the rats in the training group had significantly smaller number of apoptotic neurons in CA1 area of the hippocampus (P<0.05). (3) NeuN immunohistochemistry showed that number of NeuN positive cells of the vehicle control group was significantly smaller than that of the control group, while that of the training group was significantly larger than that of the vehicle group (P<0.05). (4) Western blotting showed that MDA content significantly decreased, glutathione content significantly increased, and SOD and glutathion peroxidase activities significantly enhanced in the training group as compared with those in the vehicle group (P<0.05); The expressions of Bcl-2, BDNF, p-Akt/Akt, p- calmodulin-dependent kinase IIa (CaMKII)/CaMKII and p-cAMP-response element binding protein(CREB)/CREB were significant up-regulated, and caspase-3 and Bax expressions were significant down-regulated in the training group as compared with those in the vehicle group (P<0.05). Conclusion The treadmill exercise may improve the spatial learning and memory abilities of autism rats; treadmill exercise strengthens the brain antioxidant ability and plays a neuroprotective role in hippocampal neuronal cells. Key words: Autism; Treadmill exercise; Learning and memory; Hippocampus