Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice.
Post-operative cognitive dysfunction (POCD) 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 β-amyloid (Aβ) 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 Aβ accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2α. γ-Secretase inhibitor compound E ameliorated the surgery-induced brain Aβ 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 Aβ accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD.
1] Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060 [2].
Zhipeng
Z
Xu
1] Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060 [2].
Yuanlin
Y
Dong
1] Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060 [2] Department of Anesthesia, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China 100020.
Hui
H
Wang
Department of Anesthesia, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115.
Deborah J
DJ
Culley
Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115.
Edward R
ER
Marcantonio
Department of Anesthesia, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115.
Gregory
G
Crosby
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060.
Rudolph E
RE
Tanzi
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060.
Yiying
Y
Zhang
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060.
Zhongcong
Z
Xie
D000005:Abdomen / Q000473:pathology / Q000601:surgery; D000368:Aged; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000768:Anesthesia, General / Q000009:adverse effects*; D000818:Animals; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011183:Postoperative Complications / Q000473:pathology*
D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases