Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice
Isoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival...
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| Format: | Article |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2020.620946/full |
| _version_ | 1818662358066659328 |
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| author | Pengfei Liu Quansheng Gao Lei Guan Weixuan Sheng Yanting Hu Teng Gao Jingwen Jiang Yongxing Xu Hui Qiao Xinying Xue Sanhong Liu Tianzuo Li |
| author_facet | Pengfei Liu Quansheng Gao Lei Guan Weixuan Sheng Yanting Hu Teng Gao Jingwen Jiang Yongxing Xu Hui Qiao Xinying Xue Sanhong Liu Tianzuo Li |
| author_sort | Pengfei Liu |
| collection | DOAJ |
| description | Isoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival and inflammation. Besides, atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts neuroprotective effects. Thus, this study aimed to explore the influence of atorvastatin on isoflurane-induced neurodegeneration and underlying mechanisms. Aged C57BL/6 mice (20 months old) were exposed to isoflurane (1.5%) anesthesia for 6 h. Atorvastatin (5, 10, or 20 mg/kg body weight) was administered to the mice for 7 days. Atorvastatin attenuated the isoflurane-induced generation of ROS and apoptosis. Western blotting revealed a decrease in cleaved caspase-9 and caspase-3 expression in line with ROS levels. Furthermore, atorvastatin ameliorated the isoflurane-induced activation of p38MAPK/ATF-2 signaling. In a cellular study, we proved that isoflurane could induce oxidative stress and inflammation by activating the p38MAPK/ATF-2 pathway in BV-2 microglia cells. In addition, SB203580, a selected p38MAPK inhibitor, inhibited the isoflurane-induced inflammation, oxidative stress, and apoptosis. The results implied that p38MAPK/ATF-2 was a potential target for the treatment of postoperative cognitive dysfunction. |
| first_indexed | 2024-12-17T04:59:41Z |
| format | Article |
| id | doaj.art-28f7466fcf5844a8889631ad3e8d0ae5 |
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| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-17T04:59:41Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-28f7466fcf5844a8889631ad3e8d0ae52022-12-21T22:02:36ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-01-011210.3389/fnagi.2020.620946620946Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged MicePengfei Liu0Quansheng Gao1Lei Guan2Weixuan Sheng3Yanting Hu4Teng Gao5Jingwen Jiang6Yongxing Xu7Hui Qiao8Xinying Xue9Sanhong Liu10Tianzuo Li11Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Operational Medicine, Tianjin Institute of Environmental and Operational Medicine, Tianjin, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Nephrology, Chinese PLA Strategic Support Force Characteristic Medical Center, Beijing, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaIsoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival and inflammation. Besides, atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts neuroprotective effects. Thus, this study aimed to explore the influence of atorvastatin on isoflurane-induced neurodegeneration and underlying mechanisms. Aged C57BL/6 mice (20 months old) were exposed to isoflurane (1.5%) anesthesia for 6 h. Atorvastatin (5, 10, or 20 mg/kg body weight) was administered to the mice for 7 days. Atorvastatin attenuated the isoflurane-induced generation of ROS and apoptosis. Western blotting revealed a decrease in cleaved caspase-9 and caspase-3 expression in line with ROS levels. Furthermore, atorvastatin ameliorated the isoflurane-induced activation of p38MAPK/ATF-2 signaling. In a cellular study, we proved that isoflurane could induce oxidative stress and inflammation by activating the p38MAPK/ATF-2 pathway in BV-2 microglia cells. In addition, SB203580, a selected p38MAPK inhibitor, inhibited the isoflurane-induced inflammation, oxidative stress, and apoptosis. The results implied that p38MAPK/ATF-2 was a potential target for the treatment of postoperative cognitive dysfunction.https://www.frontiersin.org/articles/10.3389/fnagi.2020.620946/fullmitogen activated protein kinasesneuronal degenerationreactive oxygen speciesisofluraneatorvastatinaging |
| spellingShingle | Pengfei Liu Quansheng Gao Lei Guan Weixuan Sheng Yanting Hu Teng Gao Jingwen Jiang Yongxing Xu Hui Qiao Xinying Xue Sanhong Liu Tianzuo Li Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice Frontiers in Aging Neuroscience mitogen activated protein kinases neuronal degeneration reactive oxygen species isoflurane atorvastatin aging |
| title | Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice |
| title_full | Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice |
| title_fullStr | Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice |
| title_full_unstemmed | Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice |
| title_short | Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice |
| title_sort | atorvastatin attenuates isoflurane induced activation of ros p38mapk atf2 pathway neuronal degeneration and cognitive impairment of the aged mice |
| topic | mitogen activated protein kinases neuronal degeneration reactive oxygen species isoflurane atorvastatin aging |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2020.620946/full |
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