1. Anesthesia/Surgery Induces Cognitive Impairment in Female Alzheimer’s Disease Transgenic Mice
- Author
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Yiying Zhang, Ce Zhang, Yuanlin Dong, Zhongcong Xie, Guoqing Zhao, and Yuan Shen
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Synaptophysin ,Hippocampus ,Mice, Transgenic ,Context (language use) ,Hippocampal formation ,Sevoflurane ,Cyclophilins ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,Conditioning, Psychological ,medicine ,Animals ,Cognitive Dysfunction ,Fear conditioning ,Freezing Reaction, Cataleptic ,Anesthetics ,Laparotomy ,Sex Characteristics ,biology ,business.industry ,General Neuroscience ,Fear ,General Medicine ,medicine.disease ,Surgery ,Disease Models, Animal ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,Anesthesia ,biology.protein ,Female ,Geriatrics and Gerontology ,business ,Disks Large Homolog 4 Protein ,Postoperative cognitive dysfunction ,Cyclophilin D ,030217 neurology & neurosurgery ,Abdominal surgery ,medicine.drug - 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.
- Published
- 2017