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Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice

BACKGROUND: Postoperative cognitive dysfunction (POCD) can be described as a clinical phenomenon characterized by cognitive impairment in patients, particularly elderly patients, after anesthesia and surgery. Researchers have focused on the probable effect of general anesthesia drugs on cognitive fu...

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Autores principales: Shen, Qihong, Jiang, Yanyu, Jia, Xiaoyu, Zhou, Xuyan, Zhou, Qing-he
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Brieflands 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990511/
https://www.ncbi.nlm.nih.gov/pubmed/36896324
http://dx.doi.org/10.5812/ijpr-133971
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author Shen, Qihong
Jiang, Yanyu
Jia, Xiaoyu
Zhou, Xuyan
Zhou, Qing-he
author_facet Shen, Qihong
Jiang, Yanyu
Jia, Xiaoyu
Zhou, Xuyan
Zhou, Qing-he
author_sort Shen, Qihong
collection PubMed
description BACKGROUND: Postoperative cognitive dysfunction (POCD) can be described as a clinical phenomenon characterized by cognitive impairment in patients, particularly elderly patients, after anesthesia and surgery. Researchers have focused on the probable effect of general anesthesia drugs on cognitive functioning status in older adults. Melatonin is an indole-type neuroendocrine hormone with broad biological activity and potent anti-inflammatory, anti-apoptotic, and neuroprotective effects. This study investigated the effects of melatonin on cognitive behavior in aged mice anesthetized with sevoflurane. In addition, melatonin’s molecular mechanism was determined. OBJECTIVES: This study aimed to investigate the mechanisms of melatonin against sevoflurane-induced neurotoxicity. METHODS: A total of 94 aged C57BL/6J mice were categorized into different groups, namely control (control + melatonin (10 mg/kg)), sevoflurane (sevoflurane + melatonin (10 mg/kg)), sevoflurane + melatonin (10 mg/kg) + phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor LY294002 (30 mg/kg), and sevoflurane + melatonin (10 mg/kg) + mammalian target of rapamycin (mTOR) inhibitor (10 mg/kg). The open field and Morris water maze tests were utilized to assess the neuroprotective effects of melatonin on sevoflurane-induced cognitive impairment in aged mice. The expression levels of the apoptosis-linked proteins, PI3K/Akt/mTOR signaling pathway, and pro-inflammatory cytokines in the brain’s hippocampus region were determined using the Western blotting technique. The apoptosis of the hippocampal neurons was observed using the hematoxylin and eosin staining technique. RESULTS: Neurological deficits in aged, sevoflurane-exposed mice were significantly decreased after melatonin treatment. Mechanistically, melatonin treatment restored sevoflurane-induced down-regulated PI3K/Akt/mTOR expression and significantly attenuated sevoflurane-induced apoptotic cells and neuroinflammation. CONCLUSIONS: The findings of this study have highlighted the neuroprotective effect of melatonin on sevoflurane-induced cognitive impairment via regulating the PI3K/Akt/mTOR pathway, which might be effective in the clinical treatment of elderly patients with anesthesia-induced POCD.
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spelling pubmed-99905112023-03-08 Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice Shen, Qihong Jiang, Yanyu Jia, Xiaoyu Zhou, Xuyan Zhou, Qing-he Iran J Pharm Res Research Article BACKGROUND: Postoperative cognitive dysfunction (POCD) can be described as a clinical phenomenon characterized by cognitive impairment in patients, particularly elderly patients, after anesthesia and surgery. Researchers have focused on the probable effect of general anesthesia drugs on cognitive functioning status in older adults. Melatonin is an indole-type neuroendocrine hormone with broad biological activity and potent anti-inflammatory, anti-apoptotic, and neuroprotective effects. This study investigated the effects of melatonin on cognitive behavior in aged mice anesthetized with sevoflurane. In addition, melatonin’s molecular mechanism was determined. OBJECTIVES: This study aimed to investigate the mechanisms of melatonin against sevoflurane-induced neurotoxicity. METHODS: A total of 94 aged C57BL/6J mice were categorized into different groups, namely control (control + melatonin (10 mg/kg)), sevoflurane (sevoflurane + melatonin (10 mg/kg)), sevoflurane + melatonin (10 mg/kg) + phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor LY294002 (30 mg/kg), and sevoflurane + melatonin (10 mg/kg) + mammalian target of rapamycin (mTOR) inhibitor (10 mg/kg). The open field and Morris water maze tests were utilized to assess the neuroprotective effects of melatonin on sevoflurane-induced cognitive impairment in aged mice. The expression levels of the apoptosis-linked proteins, PI3K/Akt/mTOR signaling pathway, and pro-inflammatory cytokines in the brain’s hippocampus region were determined using the Western blotting technique. The apoptosis of the hippocampal neurons was observed using the hematoxylin and eosin staining technique. RESULTS: Neurological deficits in aged, sevoflurane-exposed mice were significantly decreased after melatonin treatment. Mechanistically, melatonin treatment restored sevoflurane-induced down-regulated PI3K/Akt/mTOR expression and significantly attenuated sevoflurane-induced apoptotic cells and neuroinflammation. CONCLUSIONS: The findings of this study have highlighted the neuroprotective effect of melatonin on sevoflurane-induced cognitive impairment via regulating the PI3K/Akt/mTOR pathway, which might be effective in the clinical treatment of elderly patients with anesthesia-induced POCD. Brieflands 2023-01-24 /pmc/articles/PMC9990511/ /pubmed/36896324 http://dx.doi.org/10.5812/ijpr-133971 Text en Copyright © 2023, Author(s) https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
spellingShingle Research Article
Shen, Qihong
Jiang, Yanyu
Jia, Xiaoyu
Zhou, Xuyan
Zhou, Qing-he
Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice
title Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice
title_full Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice
title_fullStr Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice
title_full_unstemmed Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice
title_short Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice
title_sort amelioratory effect of melatonin on cognition dysfunction induced by sevoflurane anesthesia in aged mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990511/
https://www.ncbi.nlm.nih.gov/pubmed/36896324
http://dx.doi.org/10.5812/ijpr-133971
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