Affiliations: [a] Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| [b] Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China
| [c] Department of Anesthesiology and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Correspondence:
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Correspondence to: Junyan Yao, Department of Anesthesiology and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Tel.: +86 189 1829 1693; E-mail: junyanyao@shsmu.edu.cn.
Abstract: Background:Our previous studies indicated that anesthesia/surgery could aggravate cognitive impairment and tau pathology in female 5XFAD transgenic (Tg) mice. However, it is unknown whether there are sex differences in the susceptibility of developing postoperative cognitive dysfunction in 5XFAD Tg mice. Objective:In this study, we aim to determine whether anesthesia/surgery can have different effects on female and male 5XFAD Tg mice, and to explore the underpinning mechanisms. Methods:The mice received abdominal surgery under isoflurane anesthesia. Morris water maze was used to assess the cognitive function. Hippocampal levels of p-tau (AT8), p-IRS1 (Ser612), IRS1, p-GSK3β (Tyr216), and p-GSK3β (Ser9) at postoperative day 1 were evaluated by western blot assays. Results:Anesthesia/surgery exaggerated cognitive impairment and tau pathology in female, but not male 5XFAD Tg mice. The anesthesia/surgery led to elevated hippocampus protein levels of p-IRS1 (Ser612)/IRS1 ratio and p-GSK3β (Tyr216) and reduced hippocampus protein levels of p-GSK3β (Ser9) in female, but not male 5XFAD Tg mice. Conclusions:This study demonstrated that female 5XFAD Tg mice were more susceptible to anesthesia/surgery-induced cognitive deterioration and tau pathology aggravation, potentially due to female-specific brain insulin resistance.
Keywords: Alzheimer’s disease, anesthesia/surgery, brain insulin resistance, cognitive dysfunction, sex difference, tau
