IMR Press / FBL / Volume 27 / Issue 11 / DOI: 10.31083/j.fbl2711303
Open Access Original Research
SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway
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1 Department of Anesthesiology, Peking University People's Hospital, 100044 Beijing, China
2 Department of Anesthesiology, Peking University Hospital of Stomatology, 100081 Beijing, China
3 Birth Defects Prevention and Control Technology Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, 100853 Beijing, China
4 Department of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, 100191 Beijing, China
5 Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, 100040 Beijing, China
*Correspondence: (Junliang Yuan); (Dongliang Zhang)
These authors contributed equally.
Academic Editor: Igor Lavrov
Front. Biosci. (Landmark Ed) 2022, 27(11), 303;
Submitted: 1 August 2022 | Revised: 27 September 2022 | Accepted: 12 October 2022 | Published: 8 November 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Postoperative cognitive dysfunction (POCD) is a common complication after surgery and anesthesia. In this study, we aimed to determine the neuroprotective mechanism of Sirtuin 3 (SIRT3) and propofol in POCD. Methods: The cognitive dysfunction models in C57BL/6J mice were induced and treated, then cognitive function of mice were tested using morris water maze and novel object recognition tests. Primary neurons were stimulated by lipopolysaccharide (LPS) to mimic neuroinflammation during POCD. Meanwhile, cells were treated with propofol. 3-methyladenine (3-MA) was administrated to inhibit autophagy in neurons. SIRT3 overexpression vector was constructed to upregulate SIRT3. Biomarker changes in inflammation, oxidative stress and autophagy were determined in vivo and in vitro. Results: Propofol enhanced the spatial cognitive ability and novel objective recognition of POCD mice. Inflammation and oxidative stress were observed in the hippocampus, which were inhibited by propofol treatment. During POCD, SIRT3 expression and autophagy in the hippocampus was decreased; propofol activated autophagy and upregulated SIRT3. In LPS-stimulated neurons, SIRT3 upregulation enhanced the anti-inflammation and anti-oxidative stress roles of propofol; SIRT3 elevated propofol-activated autophagy in neurons undergoing LPS administration. Moreover, 3-MA reversed propofol-induced biomarker changes in inflammation, oxidative stress and autophagy in LPS-stimulated neurons. In POCD mice, SIRT3 upregulation enhanced the cognitive function during propofol treatment; SIRT3 overexpression elevated the inhibitory role of propofol in inflammation, oxidative stress and autophagy. AMPK/mTOR pathway was activated in response to propofol treatment and SIRT3 enhanced the signaling activation. Conclusions: SIRT3 enhances the protective effect of propofol on POCD by triggering autophagy that eliminates oxidative stress and inhibits the production of pro-inflammatory cytokines.

postoperative cognitive dysfunction

1. SIRT3 mediated autophagy activation via AMPK/mTOR pathway during propofol treatment.
2. SIRT3 enhanced the inhibitory effect of propofol on neuroinflammation via activating autophagy.
3. SIRT3 enhanced the protective effect of propofol on postoperative cognitive dysfunction.

82071552/National Natural Science Foundation of China
Fig. 1.
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