Treadmill exercise improves motor and memory functions in cerebral palsy rats through activation of PI3K-Akt pathway.

Abstract

Cerebral palsy (CP) is a chronic disorder characterized by physical disability and disruption of brain function. We evaluated the effects of treadmill exercise on motor and memory functions in relation with phosphatidylinositol 3-kinase (PI3K)-Akt pathway using CP rat model. Rota-rod test, step-down avoidance task, 5-bromo-2′-deoxyuridine (BrdU) immunohistochemistry, and western blot for synapsin I, postsynaptic density-95 (PSD-95), PI3K, Akt, and glycogen synthase kinase-3β (GSK-3β) were performed. CP was induced by maternal lipopolysaccharide (LPS)-injection with sensorimotor restriction. Five weeks after birth, the rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 4 weeks. Motor and memory functions were impaired in the LPS-induced CP rats and tread-mill exercise increased motor and memory functions in the CP rats. Cell proliferation in the hippocampus was suppressed in the LPS-induced CP rats and treadmill exercise increased hippocampal cell proliferation in the CP rats. Expressions of synapsin I, PSD-95, phosphorylated (p)-PI3K, and p-Akt were decreased in the LPS-induced CP rats and treadmill exercise enhanced the expressions of synapsin I, PSD-95, p-PI3K, and p-Akt in the CP rats. GSK-3β expression was increased in the LPS-induced CP rats and treadmill exercise suppressed GSK-3β expression in the CP rats. The present results suggest that treadmill exercise might improve motor and memory functions through activation of PI3K-Akt pathway.