MitoQ reducing sevoflurane-induced cognitive dysfunction by modulating mitochondrial dysfunction

Postoperative neurocognitive disorders (POCD) is a common post-surgical complication that severely impacts patients' quality of life, with perioperative anesthesia exposure recognized as a key contributing factor. This study focused on sevoflurane-induced cognitive dysfunction which is a model isolating anesthesia-related mechanisms of POCD, to investigate the therapeutic effect of mitoquinone (mitoQ), a mitochondrial-targeted antioxidant, in counteracting anesthesia-driven cognitive decline.

Aged C57 male mice (18 weeks old) were treated with mitoQ prior to sevoflurane exposure, spatial learning ability was assessed in each group using a water maze, mitochondrial function, oxidative stress, inflammation, autophagy, and apoptosis were observed in the brain tissues and various cell lines of the mice using WB, immunofluorescence, or flow cytometry, and metabolism of the HT22 cells was detected using the Seahorse MDA and SOD kits to detect the level of oxidative stress in HT22 cells.

Behavioral experiments demonstrated that sevoflurane exposure resulted in spatial memory dysfunction in mice, and mitoQ treatment attenuated this cognitive dysfunction; mechanistically, mitoQ reduced Mfn1, Mfn2 expression in HT22 cells of the SEV treatment group in a dose-dependent manner, increased Drp1 and Fis1 expression to maintain mitochondrial function, and inhibited excessive autophagy by reducing LC3 and P62 expression to inhibit excessive autophagy, reduced NLRP3 and ASC protein expression in BV2 cells of SEV treatment group to attenuate inflammation, and thus reduced Cleaved caspase1 and GSDMD expression in whole brain tissues, suggesting that apoptosis was attenuated.

MitoQ attenuates apoptosis by modulating mitochondrial dynamics, oxidative stress, inflammation, and autophagy to achieve therapeutic prevention of sevoflurane-induced cognitive dysfunction in aged mice are confirmatory of the potential of mitoQ in preventing POCD in elderly patients.