Integrative metabolomics and transcriptomics analysis of hippocampus reveals taurine metabolism and sphingolipid metabolism dysregulation associated with sleep deprivation-induced memory impairment

Sleep plays a crucial role in restoring and repairing the body, consolidating memory, regulating emotions, maintaining metabolic and so on. Sleep deprivation is known to impair cognitive functions. In this study, we investigated the mechanisms underlying memory impairment induced by sleep deprivation through a combined metabolomic and transcriptomic analysis of hippocampus. Eight-week-old mice were selected as the study subjects and the sleep deprivation chamber was used to establish a sleep deprivation model. Novel object recognition tests (NOR), and Y-maze tests were used to assess the behavioral outcomes in mice. The hippocampus were extracted and studied using the untargeted metabolomics or transcriptomics high-throughput sequencing method. An integrative analysis was conducted to elucidate the metabolic and genetic changes. Behavioral tests showed that sleep-deprived mice exhibited memory impairment. Metabolomic analysis identified 84 differentially expressed metabolites (DEMs), including 12 under the positive ion mode and 72 under the negative ion mode. The analysis revealed that sleep deprivation caused abnormalities in several metabolic pathways, with particularly pronounced effects observed in glycerophospholipid metabolism, linoieic acid metabolism, alanine, aspartate, glutamate metabolism, taurine and hypotaurine metabolism, and purine metabolism. While transcriptomic analysis releaved 97 differentially expressed genes (DEGs) (51 were down-regulated and 46 were up-regulated DEGs). Integrative analysis of the metabolomic and transcriptomic identified profiles showed that sleep deprivation may regulate taurine and hypotaurine metabolism and sphingolipid metabolism, there by influencing memory. Our results prompt severe metabolic disturbances occur in the hippocampus with sleep deprivation in mice, which can provide a basis for the mechanism research.