Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Pengfei, Gao, Quansheng, Guan, Lei, Sheng, Weixuan, Hu, Yanting, Gao, Teng, Jiang, Jingwen, Xu, Yongxing, Qiao, Hui, Xue, Xinying, Liu, Sanhong, Li, Tianzuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840608/
https://www.ncbi.nlm.nih.gov/pubmed/33519423
http://dx.doi.org/10.3389/fnagi.2020.620946
_version_ 1783643614705876992
author Liu, Pengfei
Gao, Quansheng
Guan, Lei
Sheng, Weixuan
Hu, Yanting
Gao, Teng
Jiang, Jingwen
Xu, Yongxing
Qiao, Hui
Xue, Xinying
Liu, Sanhong
Li, Tianzuo
author_facet Liu, Pengfei
Gao, Quansheng
Guan, Lei
Sheng, Weixuan
Hu, Yanting
Gao, Teng
Jiang, Jingwen
Xu, Yongxing
Qiao, Hui
Xue, Xinying
Liu, Sanhong
Li, Tianzuo
author_sort Liu, Pengfei
collection PubMed
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.
format Online
Article
Text
id pubmed-7840608
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78406082021-01-29 Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice Liu, Pengfei Gao, Quansheng Guan, Lei Sheng, Weixuan Hu, Yanting Gao, Teng Jiang, Jingwen Xu, Yongxing Qiao, Hui Xue, Xinying Liu, Sanhong Li, Tianzuo Front Aging Neurosci Neuroscience 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. Frontiers Media S.A. 2021-01-14 /pmc/articles/PMC7840608/ /pubmed/33519423 http://dx.doi.org/10.3389/fnagi.2020.620946 Text en Copyright © 2021 Liu, Gao, Guan, Sheng, Hu, Gao, Jiang, Xu, Qiao, Xue, Liu and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Liu, Pengfei
Gao, Quansheng
Guan, Lei
Sheng, Weixuan
Hu, Yanting
Gao, Teng
Jiang, Jingwen
Xu, Yongxing
Qiao, Hui
Xue, Xinying
Liu, Sanhong
Li, Tianzuo
Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice
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 Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840608/
https://www.ncbi.nlm.nih.gov/pubmed/33519423
http://dx.doi.org/10.3389/fnagi.2020.620946
work_keys_str_mv AT liupengfei atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT gaoquansheng atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT guanlei atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT shengweixuan atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT huyanting atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT gaoteng atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT jiangjingwen atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT xuyongxing atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT qiaohui atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT xuexinying atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT liusanhong atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice
AT litianzuo atorvastatinattenuatesisofluraneinducedactivationofrosp38mapkatf2pathwayneuronaldegenerationandcognitiveimpairmentoftheagedmice