NLRP3 inflammasome activation mediates sleep deprivation-induced pyroptosis in mice

Abstract

Background Sleep deprivation (SD) has many deleterious health effects, including cognitive decline, work ability decline, inadequate alertness, etc. Neuroinflammation plays an important role in sleep deprivation. However, the underlying mechanism is still unclear. Methods In the present study, we detected the activation of microglia and apoptosis of nerve cells in sleep deprivation (SD) mice model using IHC, HE staining and TUNEL apoptosis assay. RT-PCR array data were used to detect the expression of inflammatory bodies in hippocampal CA1 region after sleep deprivation, to explore how NLRP3 inflammasome regulates neuronal apoptosis and how specific signaling pathways are involved in SD-induced activation of NLRP3/pyrosis axis. Results We found the number of microglia significantly increased in SD mice, while this effect was blocked by sleep recovery. RT-PCR array data suggested that NLRP3 inflammasome, but not other inflammasomes, was obviously increased in hippocampus CA1 region after sleep deprivation. Mechanistically, we found that NLRP3 mediated the pyroptosis of neurocyte through GSDMD-dependent way , and P38 and ERK-MAPK signaling pathway is involved in SD-induced activation of NLRP3/pyroptosis axis. All these results suggested that MAPK/NLRP3 axis mediated SD-induced pyroptosis. Conclusion NLRP3 plays an important role in SD-induced neuroinflammation. Thus, NLRP3 inflammasome is expected to be a potential therapeutic target for SD-induced neuroinflammation.

Keywords

• Sleep deprivation
• NLRP3
• Pyroptosis
• MAPK