Affiliations: [a] Department of Anesthesia, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China | [b] Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
| [c] Department of Psychiatry, Tenth People’s Hospital of Tongji University, Shanghai, P.R. China
Correspondence:
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Correspondence to: Zhongcong Xie, MD, PhD, Professor of Anesthesia, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 4310, Charlestown, MA 02129-2060, USA. Tel.: +617 724 9308; Fax: +617 643 9277; E-mail: zxie@mgh.harvard.edu and Yuanlin Dong, MD, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 4310, Charlestown, MA 02129-2060, USA. Tel.: +617 724 4109; Fax: +617 643 9277; E-mail: ydong@mgh.harvard.edu.
Abstract: Anesthesia and/or surgery may promote Alzheimer’s disease (AD) by 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 (CypD KO) mice. The mice received an abdominal surgery under sevoflurane anesthesia (anesthesia/surgery). Fear Conditioning System (FCS) was used to assess the cognitive function. Hippocampal levels of synaptic marker postsynaptic density 95 (PSD-95) and synaptophysin (SVP) were measured using western blot analysis. 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, but not male, mice. The anesthesia/surgery reduced hippocampus levels of synaptic marker PSD-95 and SVP 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 CypD KO mice. 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.
