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Populations worldwide are increasingly becoming physically inactive, which is related to somatic and psychological health problems that are prevalent in modern society. Recent epidemiological studies have indicated that the associations between physical inactivity and depression are bidirectional. Numerous animal studies have demonstrated that exercise improves hippocampal function. Because the hippocampus is a pivotal brain region that exerts inhibitory control over stress responses by affecting the hypothalamus-pituitary-adrenal axis, enhanced hippocampal function by exercise can increase stress resilience, which helps prevent stress-related depression. In contrast, physical inactivity is difficult to model in animal studies, and little is known about the effects of physical inactivity on the rodent hippocampus. To fill this gap, we previously developed a mouse model of habituated voluntary wheel running cessation as a reverse intervention to control physical activity. We found that reducing physical activity by cessation of wheel running impairs hippocampal neurogenesis in mice. Thus, this review discusses the relevant literature and provides a hypothesis that physical inactivity can be a potential risk factor for stress-related depression as it increases stress vulnerability by impairing hippocampal function.

Deleterious effects of physical inactivity on the hippocampus: New insight into the increasing prevalence of stress-related depression