Exercise attenuates maternal separation-induced mood disorder-like behaviors by enhancing mitochondrial functions and neuroplasticity in the dorsal raphe.

Loss of the mother-infant relationship during early childhood affects infant development and is known to increase the infant's vulnerability to neuropsychiatric disorders throughout life. Serotonin deficits and mitochondrial dysfunction in the dorsal raphe may underlie mood disorders such as anxiety and depression. Exercise is known to have a positive effect on brain function. In this study, we investigated the effect of exercise on mitochondrial function, apoptosis, and serotonin levels in the dorsal raphe as well as behavioral changes in cases of maternal separation. Exposure to the stress of maternal separation resulted in mitochondrial dysfunction in the dorsal raphe, including impaired Ca2+ homeostasis, an increase in reactive oxygen species such as H2O2, and a decrease in the O2 respiration rate. Exposure to maternal separation stress also decreased tryptophan hydroxylase and 5-hydroxytryptamine positive cells and increased apoptosis, anxiety, and depression. The impairments in mitochondrial function, apoptosis, and serotonin in the dorsal raphe, as well as anxiety and depression, were all improved by exercise. Exercise might alter mitochondrial function, serotonin levels, and the rate of apoptosis in the dorsal raphe. Therefore, exercise might be an important non-pharmacological intervention for the prevention and treatment of the adverse effects of maternal separation.