PI3K-Akt-Wnt Pathway Is Implicated in Exercise-Induced Improvement of Short-term Memory in Cerebral Palsy Rats

Purpose Maternal lipopolysaccharide (LPS) injection induces neurodevelopmental disorders, such as cerebral palsy. Exercise activates phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway that enhances neurogenesis. Wnt ligands are also implicated in the hippocampal neurogenesis and synaptic plasticity. Glycogen synthase kinase-3β (GSK-3β) is a downstream molecule of Akt, and GSK-3β is known to modulate hippocampal neurogenesis negatively. Methods Cerebral palsy was made by maternal LPS-injection. On the 5 weeks after birth, treadmill running was applied to the rat pups of the exercise groups, for 30 minutes, 5 times a week during 6 weeks. Results Treadmill running alleviated short-term memory impairments of the cerebral palsy rat pups. Hippocampal cell proliferation was increased and hippocampal apoptosis was suppressed by treadmill running in the cerebral palsy rat pups. Hippocampal phosphorylated-PI3K/PI3K ratio, phosphorylated-Akt/Akt ratio, and Wnt expression were enhanced by treadmill running in the cerebral palsy rat pups. In contrast, hippocampal phosphorylated-GSK-3β/GSK-3β ratio and β-catenin expression were suppressed by treadmill running in the cerebral palsy rat pups. Conclusions The results of this study showed that short-term memory improvement due to treadmill running in cerebral palsy occurs via activation of the PI3K-Akt-Wnt pathway.