Effects of postnatal treadmill exercise on apoptotic neuronal cell death and cell proliferation of maternal-separated rat pups.

Early adverse experiences resulting from maternal separation may lead to neuronal cell death and they can eventually cause memory impairment. In this study, we investigated the effects of postnatal treadmill exercise on the long-term memory capability, spatial learning ability, and depressive state, on the 5-hydroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the dorsal raphe nuclei, and on the apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. The rat pups in the maternal separation groups were separated from their respective mothers on the postnatal day 14. The rat pups in the maternal separation group showed depressive state with deceased memory capability and learning ability compared to the rat pups in the maternal care group. Postnatal treadmill exercise increased memory capability and learning ability and alleviated depressive state of the rat pups in the maternal separation group. The 5-HT synthesis and TPH expression in the dorsal raphe nuclei and cell proliferation in the hippocampal dentate gyrus were significantly decreased in the maternal-separated rat pups, and postnatal treadmill exercise increased 5-HT synthesis, the TPH expression, and the cell proliferation. In contrast, apoptotic neuronal cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and postnatal treadmill exercise suppressed the maternal separation-induced apoptosis. The present results demonstrated that postnatal treadmill exercise alleviated maternal separation-induced depression with decrease of memory capability and learning ability, by suppressing apoptotic neuronal cell death and by enhancing cell proliferation.