Wnt signaling pathway is implicated in the alleviating effect of treadmill exercise on maternal separation-induced depression.

Maternal separation in the developmental stage has a negative influence on brain development and causes depression. The extracellular ligand, Wnt, and its receptors play an important role in axis formation and neural development. Exercise inhibits apoptosis, increases cell proliferation, and exerts antidepressive effect. In this study, the effect of treadmill exercise on the maternal separation-induced depression was investigated in the aspect of Wnt signaling pathway. The maternal separation started on the postnatal day 14. The rat pups in the exercise groups were forced to run on a treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. The rat pups in the maternal separation and fluoxetine-treated group were intraperitoneally injected with 5-mg/kg fluoxetine once a day from postnatal day 21 to postnatal day 34. Forced swimming test was performed to evaluate the depression level. Western blotting was performed for the expressions of Wnt signaling ligands, Wnt2 and Wnt3a, and Wnt signaling inhibitors, Dkk1, and sFRP3. Maternal separation showed depressive behaviors in the forced swimming test. Treadmill exercise alleviated depressive behaviors in the maternal separation rat pups. Expressions of Wnt2 and Wnt3a were decreased by maternal separation. Treadmill exercise alleviated maternal separation-induced reduction of Wnt2 and Wnt3a expressions. Expressions of Dkk1 and sFRP3 in the hippocampus were increased by maternal separation. Treadmill exercise alleviated maternal separation-induced reduction of Dkk1 and sFRP3 expressions. Our study demonstrated that treadmill exercise activates Wnt signaling pathway, and then exerted antidepressive effect.