SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway
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 trea...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2022-11-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711303 |
| _version_ | 1811185786326876160 |
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| author | Shang Li Yi Zhou Huaying Hu Xiaodong Wang Junjun Xu Chaobo Bai Junliang Yuan Dongliang Zhang |
| author_facet | Shang Li Yi Zhou Huaying Hu Xiaodong Wang Junjun Xu Chaobo Bai Junliang Yuan Dongliang Zhang |
| author_sort | Shang Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:36:13Z |
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| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-11T13:36:13Z |
| publishDate | 2022-11-01 |
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| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-2c2300882cfc4629a0979e4becfa056f2022-12-22T04:21:28ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-11-01271130310.31083/j.fbl2711303S2768-6701(22)00663-3SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR PathwayShang Li0Yi Zhou1Huaying Hu2Xiaodong Wang3Junjun Xu4Chaobo Bai5Junliang Yuan6Dongliang Zhang7Department of Anesthesiology, Peking University People's Hospital, 100044 Beijing, ChinaDepartment of Anesthesiology, Peking University Hospital of Stomatology, 100081 Beijing, ChinaBirth Defects Prevention and Control Technology Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, 100853 Beijing, ChinaDepartment of Anesthesiology, Peking University Hospital of Stomatology, 100081 Beijing, ChinaDepartment of Anesthesiology, Peking University People's Hospital, 100044 Beijing, ChinaDepartment of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, 100191 Beijing, ChinaDepartment of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, 100191 Beijing, ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, 100040 Beijing, ChinaBackground: 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.https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711303postoperative cognitive dysfunctionsirt3propofolautophagy |
| spellingShingle | Shang Li Yi Zhou Huaying Hu Xiaodong Wang Junjun Xu Chaobo Bai Junliang Yuan Dongliang Zhang SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway Frontiers in Bioscience-Landmark postoperative cognitive dysfunction sirt3 propofol autophagy |
| title | SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway |
| title_full | SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway |
| title_fullStr | SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway |
| title_full_unstemmed | SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway |
| title_short | SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway |
| title_sort | sirt3 enhances the protective role of propofol in postoperative cognitive dysfunction via activating autophagy mediated by ampk mtor pathway |
| topic | postoperative cognitive dysfunction sirt3 propofol autophagy |
| url | https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711303 |
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