Metformin Ameliorates Postoperative Cognitive Dysfunction through Regulation of the AMPK/SIRT1 Pathway

Peiyu Jia; Ji Che; Junfeng Zhang; Haibing Li; Quanhong Zhou; Yong Guo

doi:10.31083/j.jin2205110

Journal of Integrative Neuroscience (Aug 2023)

Metformin Ameliorates Postoperative Cognitive Dysfunction through Regulation of the AMPK/SIRT1 Pathway

Peiyu Jia,
Ji Che,
Junfeng Zhang,
Haibing Li,
Quanhong Zhou,
Yong Guo

Affiliations

Peiyu Jia: Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, 200040 Shanghai, China
Ji Che: Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, 200040 Shanghai, China
Junfeng Zhang: Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China
Haibing Li: Department of Anesthesiology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 20092 Shanghai, China
Quanhong Zhou: Department of Critical Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China
Yong Guo: Department of Critical Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China

DOI: https://doi.org/10.31083/j.jin2205110
Journal volume & issue: Vol. 22, no. 5
p. 110

Abstract

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Background: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The purpose of this study was to investigate the mechanism through which metformin improves postoperative cognitive function. Methods: In the in vivo experiment, 18-month-old Sprague–Dawley (SD) rats were randomly divided into four groups (n = 12 in each group): the control, metformin, operation, and operation plus metformin groups. The animals were pretreated with metformin by gavage once daily for two weeks. The Morris water maze (MWM) was used to measure cognitive ability. In the in vitro experiment, BV2 cells were divided into five groups: the control, metformin, lipopolysaccharide (LPS), LPS plus metformin, and LPS plus metformin plus compound C groups. We stimulated microglia with LPS (500 ng/mL). Immunofluorescence and Western blotting were used to assess ROS (reactive oxygen species) levels, autophagy-associated protein levels and adenosine monophosphate-activated protein kinase (AMPK)/regulator factor 2-related enzyme 1 (SIRT1) signaling pathway activity in the rat cortex and microglial cells. Results: In the MWM test, the metformin-pretreated rats spent a higher proportion of time in the target quadrant. Immunofluorescence showed that the fluorescence intensity of LC3 in the cortex was increased in rats pretreated with metformin. Western blotting indicated that metformin upregulated the expression of autophagy-related and AMPK/SIRT1 signaling pathway-related proteins in the cortex after surgery. By activating the AMPK/SIRT1 signaling pathway in vitro, metformin reduced microglial activation and oxidative stress and promoted autophagy. Conclusions: Through the AMPK/SIRT1 pathway, metformin can boost autophagy and reduce oxidative stress in cortical microglia in older rats, in turn improving postoperative cognitive function.

Published in Journal of Integrative Neuroscience

ISSN: 0219-6352 (Print); 1757-448X (Online)
Publisher: IMR Press
Country of publisher: Singapore
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.imrpress.com/journal/JIN

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