0285 Preventative Voluntary Exercise Ameliorate Synaptic-Pruning Defects on Sleep-Deprived Adolescent

Abstract

Abstract Introduction Since adolescent is a critical period for brain development, adequate sleep during this period is essential to cognitive performance as well as the psychological health in later life. Emerging evidence on sleep-deprived animal models has detailed the impacts of sleep loss on the developing brain. For instance, our previous study demonstrated that 72 h sleep deprivation (SD) disrupted microglia-mediated synaptic refinement in the dentate gyrus (DG). Physical exercise is proved to counteract the harmful consequences of various stress or neurodegenerative models by modulating microglial function. Therefore, we hypothesized that physical exercise might be a preventive intervention to rescue the failure of synaptic pruning and microglial function after SD in adolescent mice. Methods C57/BL6 male mice 3 weeks were assigned to the home cage (HC), home cage with voluntary exercise (HC+VE), sleep deprivation (SD), or sleep deprivation with voluntary exercise (SD+VE) group. In the groups with VE, a running wheel was placed in the cage 11 days before the SD paradigm. Following 72 h SD, animals were subjected to a short-term memory test or sacrificed directly for further examination. Results Our results showed that impaired memory performance was reversed in sleep-deprived mice after VE. Also, the SD+VE group exhibited less dendritic spine density compared to the SD group, implying VE rescue the synaptic pruning defect after SD. Greater microglia phagocytic ability, characterized by increased internalized postsynaptic materials and lysosomal structure within individual microglia, were observed in the SD+VE compared to the SD group. We also investigated the mRNA expression of microglia-specific receptors critical to developmental synaptic refinement and found an upregulation of CX3CR1 expression in both HC+VE and SD+VE compared to sedentary groups. Conclusion Here we provided evidence featuring that developmental VE significantly alleviated the SD-induced memory defects. Moreover, the SD-induced synaptic pruning impairment and microglial maladaptation were also prevented by the VE regimen, suggesting that physical exercise is a possible therapeutic interventions to the cognitive performance as well as the developmental trajectories to the adolescent brain under the influence of sleep insufficiency. Support Supported by the Ministry of Science and Technology of the Republic of China (Grant number: 104-2314-B-002-129-MY4).