Research Paper Volume 12, Issue 1 pp 844—865

Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium

Yayuan Lu 1, , Lei Chen 1, , Jishi Ye 2, , Chang Chen 1, , Ying Zhou 1, , Ke Li 1, , Zongze Zhang 1, , Mian Peng 1, ,

  • 1 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China
  • 2 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China

received: September 10, 2019 ; accepted: December 24, 2019 ; published: January 12, 2020 ;

https://doi.org/10.18632/aging.102659
How to Cite

Copyright © 2020 Lu 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

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.

Abbreviations

POD: Postoperative delirium; DISC1: Disrupted in schizophrenia 1; Drp1: Dynamin-related protein 1; Mfn2: Mitofusin 2; ROS: Reactive oxygen species; SOD: Superoxide dismutase; ATP: Adenosine triphosphate; MMP: Mitochondrial membrane potential; PSD-95: Postsynaptic density protein 95; BDNF: Brain-derived neurotrophic factor; PBS: Phosphate-buffered saline; ITI: Inter-trial interval; OXPHOS: Oxidative phosphorylation; mPTP: mitochondrial permeability transition pore; CAM: Confusion Assessment Method.