Voluntary exercise ameliorates synaptic pruning deficits in sleep-deprived adolescent mice

Adolescence is a critical period for brain development and adequate sleep during this period is essential for physical function and mental health. Emerging evidence has detailed the neurological impacts of sleep insuffi-ciency on adolescents, as was unveiled by our previous study, microglia, one of the crucial contributors to synaptic pruning, is functionally disrupted by lack of sleep. Here, we provided evidence featuring the protective effect and the underlying mechanisms of voluntary exercise (VE) on microglial functions in an adolescent 72 h sleep deprivation (SD) model. We identified that the aberrant hippocampal neuronal activity and impaired short -term memory performance in sleep-deprived mice were prevented by 11 days of VE. VE significantly normalized the SD-induced dendritic spine increment and maintained the microglial phagocytic ability in sleep-deprived mice. Moreover, we found that the amendment of the noradrenergic signal in the central nervous system may explain the preventative effects of VE on the abnormalities of microglial and neuronal functions caused by SD. These data suggested that VE may confer protection to the microglia-mediated synaptic pruning in the sleep-deprived adolescent brains. Therefore, physical exercise could be a beneficial health practice for the adoles-cents that copes the adverse influence of inevitable sleep insufficiency.