Resveratrol Improves Cognitive Function in Sleep‐Deprived Mice by Inhibiting p38 <scp>MAPK</scp> Signaling Pathway

Resveratrol (RES) is a naturally occurring polyphenolic compound possessing neuroprotective properties. This study aims to examine the potential of RES to ameliorate sleep disorder-associated cognitive deficits induced by sleep deprivation (SD) in mice. Adult male C57/BL6 mice were subjected to SD for 72 h, and RES were administrated. Behavioral tests were performed to quantify the cognitive behaviors. RNA-sequencing coupled with bioinformatic analysis was executed to examine gene expression patterns in the hippocampus. Furthermore, the levels of apoptosis and synaptic plasticity were measured by western blotting and histological staining techniques, including the TUNEL and Nissl methods. Morris water maze, novel object recognition and open field tests demonstrated that RES swiftly attenuated the cognitive impairment induced by SD. RNA-sequencing indicated that the mitogen-activated protein kinase (MAPK) pathways were significantly downregulated by RES administration following SD. Additionally, the impaired synaptic plasticity and apoptosis elicited by SD in the hippocampus were improved by RES. SD causes cognitive dysfunction and hippocampal neuronal damage in mice. Treatment with RES improves cognitive function and attenuates neuronal damage in the hippocampus of sleep-deprived mice. Furthermore, the MAPK signaling pathway has been identified as a pivotal target in these neuroprotective effects. These findings will contribute to providing theoretical support for dietary supplementation of RES to prevent or improve cognitive dysfunction caused by sleep problems.