Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus

Abstract Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti‐inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation‐induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty‐two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro‐inflammatory cytokines and Sirt1/miR‐134 pathway‐related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation‐induced learning and memory impairment, elevated interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α levels, and decreased brain‐derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein‐95, and synaptophysin levels by activating the Sirt1/miR‐134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation‐induced cognitive dysfunction by reducing pro‐inflammatory cytokines and improving synaptic function via the Sirt1/miR‐134 pathway.