Sleep deprivation is closely associated with neuroinflammation and cognitive dysfunction, yet its underlying molecular mechanisms remain incompletely understood. Aquaporin-1 (AQP1) has been implicated in microglial regulation, but its role in chronic sleep deprivation (CSD)–induced cognitive impairment remains unclear. A chronic sleep deprivation (CSD) mouse model and an in vitro BV2 microglial inflammation model were established. Learning and memory functions were assessed using the Y-maze, novel object recognition, and Morris water maze tests. Transcriptomic sequencing was performed to identify key regulatory genes. AQP1 expression, NLRP3 inflammasome–related responses, microglial polarization, hippocampal pathology, and neuroinflammatory responses were systematically evaluated using molecular, histological, and immunological approaches. In addition, high-throughput virtual screening and molecular dynamics simulations were employed to analyze the potential association between curcumin and AQP1. CSD induced significant impairments in learning and memory, accompanied by hippocampal neuronal injury and neuroinflammatory activation. Transcriptomic analysis revealed that AQP1 was markedly upregulated in the hippocampus of CSD mice and was predominantly localized in microglia. AQP1 knockdown significantly ameliorated CSD-induced cognitive deficits and neuronal damage was accompanied by reduced NLRP3 inflammasome–related readouts, and promoted microglial polarization toward the M2 phenotype, these effects were largely reversed by the NLRP3 agonist nigericin. Furthermore, curcumin attenuated microglial M1 polarization, reduced neuroinflammation, and improved cognitive performance, alongside changes in AQP1 expression and inflammasome-related measures. AQP1 is associated with CSD-related cognitive impairment and neuroinflammatory responses, accompanied by changes in microglial polarization and NLRP3 inflammasome–related signaling. Curcumin shows neuroprotective effects under CSD conditions; whether AQP1 is a direct molecular target requires further validation.
Xiong et al. (Mon,) studied this question.