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Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice

OBJECTIVE: Postoperative neurocognitive disorder (PND) is a main complication that is commonly seen postoperatively in elderly patients. The underlying mechanism remains unclear, although neuroinflammation has been increasingly observed in PND. Atorvastatin is a pleiotropic agent with proven anti-in...

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Autores principales: Yang, Yinan, Wei, Changwei, Liu, Jinhu, Ma, Danxu, Xiong, Chao, Lin, Dandan, Wu, Anshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232118/
https://www.ncbi.nlm.nih.gov/pubmed/32412807
http://dx.doi.org/10.1177/0300060520924251
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author Yang, Yinan
Wei, Changwei
Liu, Jinhu
Ma, Danxu
Xiong, Chao
Lin, Dandan
Wu, Anshi
author_facet Yang, Yinan
Wei, Changwei
Liu, Jinhu
Ma, Danxu
Xiong, Chao
Lin, Dandan
Wu, Anshi
author_sort Yang, Yinan
collection PubMed
description OBJECTIVE: Postoperative neurocognitive disorder (PND) is a main complication that is commonly seen postoperatively in elderly patients. The underlying mechanism remains unclear, although neuroinflammation has been increasingly observed in PND. Atorvastatin is a pleiotropic agent with proven anti-inflammatory effects. In this study, we investigated the effects of atorvastatin on a PND mouse model after peripheral surgery. MATERIAL AND METHODS: The mice were randomized into five groups. The PND models were established, and an open field test and fear condition test were performed. Hippocampal inflammatory cytokine expression was determined using ELISA. Peroxisome proliferator-activated receptor-gamma (PPARγ) expression in the hippocampus was tested using qRT-PCR and western blot analysis. RESULTS: On day 1 after surgery, inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 showed a significant increase in the hippocampus, with prominent cognitive impairment. Atorvastatin treatment improved cognitive function in the mouse model, attenuated neuroinflammation, and increased PPARγ expression in the hippocampus. However, treatment with the PPARγ antagonist GW9662 partially reversed the protective effects of atorvastatin. CONCLUSIONS: These results indicated that atorvastatin improves several hippocampal functions and alleviates inflammation in PND mice after surgery, probably through a PPARγ-involved signaling pathway.
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spelling pubmed-72321182020-05-29 Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice Yang, Yinan Wei, Changwei Liu, Jinhu Ma, Danxu Xiong, Chao Lin, Dandan Wu, Anshi J Int Med Res Pre-Clinical Research Report OBJECTIVE: Postoperative neurocognitive disorder (PND) is a main complication that is commonly seen postoperatively in elderly patients. The underlying mechanism remains unclear, although neuroinflammation has been increasingly observed in PND. Atorvastatin is a pleiotropic agent with proven anti-inflammatory effects. In this study, we investigated the effects of atorvastatin on a PND mouse model after peripheral surgery. MATERIAL AND METHODS: The mice were randomized into five groups. The PND models were established, and an open field test and fear condition test were performed. Hippocampal inflammatory cytokine expression was determined using ELISA. Peroxisome proliferator-activated receptor-gamma (PPARγ) expression in the hippocampus was tested using qRT-PCR and western blot analysis. RESULTS: On day 1 after surgery, inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 showed a significant increase in the hippocampus, with prominent cognitive impairment. Atorvastatin treatment improved cognitive function in the mouse model, attenuated neuroinflammation, and increased PPARγ expression in the hippocampus. However, treatment with the PPARγ antagonist GW9662 partially reversed the protective effects of atorvastatin. CONCLUSIONS: These results indicated that atorvastatin improves several hippocampal functions and alleviates inflammation in PND mice after surgery, probably through a PPARγ-involved signaling pathway. SAGE Publications 2020-05-15 /pmc/articles/PMC7232118/ /pubmed/32412807 http://dx.doi.org/10.1177/0300060520924251 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Pre-Clinical Research Report
Yang, Yinan
Wei, Changwei
Liu, Jinhu
Ma, Danxu
Xiong, Chao
Lin, Dandan
Wu, Anshi
Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
title Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
title_full Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
title_fullStr Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
title_full_unstemmed Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
title_short Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
title_sort atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice
topic Pre-Clinical Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232118/
https://www.ncbi.nlm.nih.gov/pubmed/32412807
http://dx.doi.org/10.1177/0300060520924251
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