Research Paper Volume 12, Issue 2 pp 1965—1986

Anesthesia and surgery induce age-dependent changes in behaviors and microbiota

Ning Liufu 1, 2, *, , Ling Liu 1, 2, *, , Shiqian Shen 3, , Zengliang Jiang 4, , Yuanlin Dong 2, , Yanyan Wang 2, 5, , Deborah Culley 6, , Gregory Crosby 6, , Minghui Cao 1, , Yuan Shen 7, , Edward Marcantonio 8, , Zhongcong Xie 2, , Yiying Zhang 2, ,

  • 1 Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province 510120, P. R. China
  • 2 Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
  • 3 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
  • 4 College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, P. R. China
  • 5 Department of Anesthesia, Shanghai 10th People’s Hospital, Anesthesia and Brain Research Institute, Tongji University, Shanghai 200072, P. R. China
  • 6 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
  • 7 Department of Psychiatry, Shanghai 10th People’s Hospital, Anesthesia and Brain Research Institute, Tongji University, Shanghai 200072, P. R. China
  • 8 Divisions of General Medicine and Primary Care and Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
* Equal contribution

received: November 19, 2019 ; accepted: January 2, 2020 ; published: January 24, 2020 ;

https://doi.org/10.18632/aging.102736
How to Cite

Copyright © 2020 Liufu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The neuropathogenesis of postoperative delirium remains mostly unknown. The gut microbiota is implicated in the pathogenesis of neurological disorders. We, therefore, set out to determine whether anesthesia/surgery causes age-dependent gut microbiota dysbiosis, changes in brain IL-6 level and mitochondrial function, leading to postoperative delirium-like behavior in mice. Female 9 or 18 months old mice received abdominal surgery under 1.4% isoflurane for two hours. The postoperative delirium-like behavior, gut microbiota, levels of brain IL-6, PSD-95 and synaptophysin, and mitochondrial function were determined by a battery of behavioral tests, 16s rRNA sequencing, ELISA, Western blot and Seahorse XFp Extracellular Flux Analyzer. Intragastric administration of Lactobacillus (10 days) and probiotic (20 days) were used to mitigate the anesthesia/surgery-induced changes. Anesthesia/surgery caused different alterations in gut microbiota, including change rate of reduction in the levels of gut lactobacillus, between the 18 and 9 months old mice. The anesthesia/surgery induced greater postoperative delirium-like behavior, increased brain IL-6 levels, decreased PSD-95 and synaptophysin levels, and mitochondrial dysfunction in 18 than 9 months old mice. Treatments with Lactobacillus and probiotic mitigated the anesthesia/surgery-induced changes. These data suggest that microbiota dysbiosis may contribute to neuropathogenesis of postoperative delirium and treatment with Lactobacillus or a probiotic could mitigate postoperative delirium.

Abbreviations

AD: Alzheimer's disease; ADRD: Alzheimer's disease and related dementias; ANOVA: analysis of variance; Aβ: beta Amyloid; BBB: blood-brain barrier; CAM: Confusion Assessment Method; IL-6: Interleukin 6; PSD-95: postsynaptic density protein 95; OUT: operational taxonomic unit; PLS-DA: partial least-squares discriminant analysis; WT: wild-type; CFU: colony-forming unit; BSA: bovine serum albumin; ADP: adenosine 5'-diphosphate; FCCP: carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; OXPHOS: oxidative phosphorylation; OCR: oxygen consumption rate; SEM: standard error of the mean; SD: standard deviation.