The Sex Effect Of Anesthesia/surgery On Cognitive Function Of Alzheimer's Disease Transgenic Mice

Objective:As anesthesia exposure was suggested to be one potential precipitating factor for postoperative cognitive dysfunction and cognitive decline is a hallmark of Alzheimer disease(AD),it was hypothesized that exposure to GAs and AD may be somehow linked.Anesthesia and/or surgery may promote Alzheimer's disease(AD)through accelerating its neuropathogenesis.Other studies showed different findings.However,the potential sex difference among these studies has not been well considered and it is unknown whether male or female AD patients are more vulnerable to develop postoperative cognitive dysfunction.We therefore set out to perform a proof of concept study to determine whether anesthesia and surgery can have different effects in male and female AD transgenic(Tg)mice,and in female AD Tg plus Cyclophilin D knockout(Cyp D KO)mice.Methods:The male and female AD Tg mice,and in female AD Tg plus Cyp D KO mice received an abdominal surgery under sevoflurane anesthesia(anesthesia/surgery).Fear Conditioning System(FCS)was used to assess the cognitive function.Hippocampus levels of synaptic marker postsynaptic density 95(PSD-95)and synaptophysin(SVP)were measured using Western blot analysis.Results:Here we showed that the anesthesia/surgery decreased the freezing time in context test of FCS at 7 days after the anesthesia/surgery in female(P = 0.0159),but not male mice(P = 0.4988).The anesthesia/surgery reduced hippocampus levels of synaptic marker PSD-95(P = 0.0071)and SVP(P = 0.0061)in female,but not male mice.The anesthesia/surgery induced neither reduction in freezing time in FCS nor decreased hippocampus levels of PSD-95 and SVP in the AD Tg plus Cyp D KO mice.Conclusion:These data suggest that the anesthesia/surgery induced a sex-dependent cognitive impairment and reduction in hippocampus levels of synaptic markers in AD Tg mice,potentially via a mitochondria-associated mechanism.These findings could promote clinical investigations to determine whether female AD patients are more vulnerable to the development of postoperative cognitive dysfunction.