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

Abstract

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.

Negative rebound in hippocampal neurogenesis following exercise cessation

“…Although physical inactivity is becoming a serious public health concern (5,55), few animal models have been developed specifically to investigate the effects of physical inactivity on brain function. Because hippocampal function is inversely linked to stress vulnerability (17), our findings led us to hypothesize that physical inactivity impairs hippocampal function and thus might increase vulnerability to stress-induced mood disorders, including depression (38). Given that typical human lifestyles are increasingly sedentary, our results might explain why the prevalence of these disorders is increasing worldwide.…”

“…However, for humans, exercise is intrinsically a health-and fitness-oriented physical activity (5), whereas in laboratory rodents, which are inherently active, voluntary wheel running may reflect their natural level of activity in the wild. Thus our model can be interpreted as an animal model of sudden decrease in daily physical activity or of physical inactivity, rather than of exercise cessation (38). Although physical inactivity is becoming a serious public health concern (5,55), few animal models have been developed specifically to investigate the effects of physical inactivity on brain function.…”

“…A low level of physical activity increases the risk for neurodegenerative and psychological disorders, including Alzheimer's disease and depressive symptoms (2,3,44), and hippocampal dysfunction is a predisposing factor for these disorders (50). Therefore, the hypothesis that a reduction in physical activity impairs hippocampal function warrants further study, which is expected to provide an alternative approach to promoting cognitive and mental health (38).…”