SESN1, as a potential target for postoperative cognitive dysfunction, attenuates sevoflurane-induced neuronal cell damage in the hippocampus

Postoperative cognitive dysfunction (POCD) is a devastating complication with long-term consequences, and new therapeutic targets and drugs are still needed for the treatment of POCD. Sestrin are a family of stress-inducing proteins that regulate cellular metabolic networks. However, the possible effects of Sestrin on POCD were still unclear. This study aimed to investigate the effects of Sestrin 1 (SESN1) in postoperative cognitive dysfunction (POCD) cell model and reveal its mechanism. We constructed an in vitro model of POCD by treating primary rat hippocampal neurons with sevoflurane. Herein, we noticed SESN1 enhanced cell viability induced by sevoflurane. Further, SESN1 improved sevoflurane-induced cell inflammation. We further found that SESN1 improved sevoflurane induced reactive oxygen species (ROS) production and inhibited apoptosis. Mechanically, SESN1 restrained NOD-like receptor thermal protein domain 3 (NLRP3) inflammasome activation and therefore suppressed POCD. In conclusion, SESN1, as a potential target for postoperative cognitive dysfunction, attenuates sevoflurane-induced neuronal cell damage in the hippocampus. These findings will provide guidance for the mechanism study of POCD and future drug development for treatment of POCD.

Postoperative cognitive dysfunction (POCD); Sestrin 1 (SESN1); Inflammation; Sevoflurane; NLRP3 inflammasome

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