Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice

作者：Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Cro**y, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong^*

来源：Scientific Reports, 2014, 4(1): 3766.

DOI：10.1038/srep03766

• NECROSIS-FACTOR-ALPHA
• AMYLOID BETA-PROTEIN
• GENERAL-ANESTHESIA
• NONCARDIAC SURGERY
• INTERFERON-GAMMA
• TRANSGENIC MICE
• MOUSE MODEL
• A-BETA
• DYSFUNCTION
• DISEASE

Post-operative cognitive dysPOCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain beta-amyloid (A beta) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The A beta accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2 alpha. gamma-Secretase inhibitor compound E ameliorated the surgery-induced brain A beta accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging-or Alzheimer gene mutation-associated A beta accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD.

• 出版日期2014-1-20
• 单位首都医科大学