Exploring the potential relationship between short sleep risks and cognitive function from the perspective of inflammatory biomarkers and cellular pathways: Insights from population-based and mice studies

AimsThe molecular mechanism of short-sleep conditions on cognition remains largely unknown. This research aimed to investigate associations between short sleep, inflammatory biomarkers and cognitive function in the US population (NHANES data 2011-2014) and explore cellular mechanisms in mice.MethodsSystemic immune-inflammation index (SII) was calculated using blood-cell based biomarkers. Further, we employed integrated bioinformatics and single-cell transcriptomics (GSE137665) to examine how short sleep exposure influenced the molecular pathways associated with inflammation in the brain. To explore the signaling pathways and biological processes of sleep deprivation, we carried out enrichment analyses utilizing the GO and KEGG databases.ResultsPopulation results showed that, compared with normal sleep group, severe short sleep was associated with lower cognitive ability in all the four tests. Moreover, a higher SII level was correlated with lower scores of cognitive tests. In mice study, elevated activation of the inflammatory pathway was observed in cell subgroups of neurons within the sleep deprivation and recovery sleep cohorts. Additionally, heightened expression of oxidative stress and integrated stress response pathways was noted in GABAergic neurons during sleep deprivation.ConclusionThis study contributed to the understanding of the influence of short sleep on cognitive function and its cellular mechanisms. Severe short sleep and higher systemic immune-inflammation index level was associated with lower cognitive ability. Additionally, heightened expression of oxidative stress and integrated stress response pathways was noted in GABAergic neurons during sleep deprivation.image