Effects of treadmill exercise on the anxiety-like behavior through modulation of GSK3β/β-catenin signaling in the maternal separation rat pup

Maternal separation causes depression and anxiety. Exercise ameliorates maternal separation-induced depression. In this study, we investigated the effect of treadmill exercise on anxiety-like behavior in relation with glycogen synthase kinase 3 beta (GSK3β)/β-catenin pathway using maternal separation rat pups. For this study, elevated plus maze test, immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT), tryptophan hydroxylase (TPH), and western blot for total GSK3β (t-GSK3β), phosphorylated GSK3β (p-GSK3β), total β-catenin (t-β-catenin), and phosphorylated β-catenin (p-β-catenin) were conducted. The rat pups in the exercise groups were scheduled to run on a treadmill for 30 min once a day for 10 days, starting on postnatal day 21. For the rat pups in the fluoxetine-treated group, fluoxetine was orally administrated once a day for 10 consecutive days, starting on postnatal day 21. Anxiety-like behavior was appeared in the rat pups by maternal separation. Maternal separation suppressed 5-HT and TPH expression in the dorsal raphe. Maternal separation suppressed phosphorylation of GSK3β and increased phosphorylation of β-catenin in the hippocampus. However, treadmill exercise and fluoxetine treatment alleviated anxiety and increased 5-HT and TPH expression in the dorsal raphe. Treadmill exercise and fluoxetine treatment also enhanced GSK3β phosphorylation and suppressed β-catenin phosphorylation in the hippocampus. In this study, alleviating effect of treadmill exercise on maternal separation-induced anxiety appeared through enhancing 5-HT expression and GSK3β phosphorylation, and then inhibiting β-catenin phosphorylation. These results showed that treadmill exercise relieves anxiety through GSK3β/β-catenin pathway. Treadmill exercise showed similar ameliorating effect on anxiety-like behavior as fluoxetine.