Electroacupuncture ameliorates surgery-induced spatial memory deficits by promoting mitophagy in rats

Jian Guo; Kun Niu; Bao-Feng Ma; Li-Na Sun; Qi-Wu Fang; Jian-Xiong An

doi:10.21037/atm-22-6262

Electroacupuncture ameliorates surgery-induced spatial memory deficits by promoting mitophagy in rats

Ann Transl Med. 2023 Jan 31;11(2):74. doi: 10.21037/atm-22-6262.

Authors

Jian Guo^#^{1

2

3}, Kun Niu^#^{2

4}, Bao-Feng Ma^{1

2}, Li-Na Sun^{1

2}, Qi-Wu Fang², Jian-Xiong An^{1

2

5}

Affiliations

¹ School of Anesthesiology, Weifang Medical University, Weifang, China.
² Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China.
³ Department of Anesthesiology, Yan'an People's Hospital, Yan'an, China.
⁴ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital and Institute, Beijing, China.
⁵ Department of Anesthesiology, Pain and Sleep Medicine, The Affiliated Hospital of Weifang Medical University, Weifang, China.

^# Contributed equally.

Abstract

Background: This study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery.

Methods: Hepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed.

Results: EA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3‑kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1β in the hippocampus (P<0.05).

Conclusions: These results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

Keywords: Perioperative neurocognitive disorders (PNDs); coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3); electroacupuncture (EA); hippocampus; reactive oxygen species (ROS).