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WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice

Anesthesia/surgery has been reported to be associated with perioperative neurocognitive disorder (PND) in patients and induces cognitive impairment in mice. Previous studies demonstrate cyclosporine A (CsA) attenuates the anesthesia/surgery-induced cognitive impairment in mice. However, CsA has immu...

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Autores principales: Lin, Jiefu, Shen, Fuyi, Lu, Jing, Liang, Feng, Zhang, Yiying, Xie, Zhongcong, Dong, Yuanlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335586/
https://www.ncbi.nlm.nih.gov/pubmed/34366827
http://dx.doi.org/10.3389/fnagi.2021.688587
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author Lin, Jiefu
Shen, Fuyi
Lu, Jing
Liang, Feng
Zhang, Yiying
Xie, Zhongcong
Dong, Yuanlin
author_facet Lin, Jiefu
Shen, Fuyi
Lu, Jing
Liang, Feng
Zhang, Yiying
Xie, Zhongcong
Dong, Yuanlin
author_sort Lin, Jiefu
collection PubMed
description Anesthesia/surgery has been reported to be associated with perioperative neurocognitive disorder (PND) in patients and induces cognitive impairment in mice. Previous studies demonstrate cyclosporine A (CsA) attenuates the anesthesia/surgery-induced cognitive impairment in mice. However, CsA has immunosuppressive effects and may not be routinely used to prevent or treat PND in patients. WS635 is a nonimmunosuppressive CsA analog. We, therefore, set out to determine whether WS635 could mitigate the anesthesia/surgery-induced cognitive impairment in mice. We performed abdominal surgery under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h in 9 month-old wild-type (WT) mice. We treated the mice with CsA (10 mg/kg) or different doses (13.2 mg/kg, 26.4 mg/kg and 52.8 mg/kg) of WS635 before and after the anesthesia/surgery. Barnes maze and fear conditioning system (FCS) were employed to evaluate the cognitive function in mice. We measured the amounts of postsynaptic density (PSD)-95, synaptophysin, and ATP in the hippocampus and cortex of the mice using western blot and ATP Colorimetric/Fluorometric Assay, respectively. We found that the treatment with 52.8 mg/kg, but not 13.2 mg/kg or 26.4 mg/kg, of WS635 attenuated the anesthesia/surgery-induced cognitive impairment in mice and the reductions in the amounts of PSD-95, synaptophysin, and ATP in the mice brain tissues. These results have established a system to study WS635 further and suggest that we need to perform more experiments to determine whether WS635 can ultimately be used as one of the interventions for PND in patients.
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spelling pubmed-83355862021-08-05 WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice Lin, Jiefu Shen, Fuyi Lu, Jing Liang, Feng Zhang, Yiying Xie, Zhongcong Dong, Yuanlin Front Aging Neurosci Neuroscience Anesthesia/surgery has been reported to be associated with perioperative neurocognitive disorder (PND) in patients and induces cognitive impairment in mice. Previous studies demonstrate cyclosporine A (CsA) attenuates the anesthesia/surgery-induced cognitive impairment in mice. However, CsA has immunosuppressive effects and may not be routinely used to prevent or treat PND in patients. WS635 is a nonimmunosuppressive CsA analog. We, therefore, set out to determine whether WS635 could mitigate the anesthesia/surgery-induced cognitive impairment in mice. We performed abdominal surgery under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h in 9 month-old wild-type (WT) mice. We treated the mice with CsA (10 mg/kg) or different doses (13.2 mg/kg, 26.4 mg/kg and 52.8 mg/kg) of WS635 before and after the anesthesia/surgery. Barnes maze and fear conditioning system (FCS) were employed to evaluate the cognitive function in mice. We measured the amounts of postsynaptic density (PSD)-95, synaptophysin, and ATP in the hippocampus and cortex of the mice using western blot and ATP Colorimetric/Fluorometric Assay, respectively. We found that the treatment with 52.8 mg/kg, but not 13.2 mg/kg or 26.4 mg/kg, of WS635 attenuated the anesthesia/surgery-induced cognitive impairment in mice and the reductions in the amounts of PSD-95, synaptophysin, and ATP in the mice brain tissues. These results have established a system to study WS635 further and suggest that we need to perform more experiments to determine whether WS635 can ultimately be used as one of the interventions for PND in patients. Frontiers Media S.A. 2021-07-21 /pmc/articles/PMC8335586/ /pubmed/34366827 http://dx.doi.org/10.3389/fnagi.2021.688587 Text en Copyright © 2021 Lin, Shen, Lu, Liang, Zhang, Xie and Dong. https://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
Lin, Jiefu
Shen, Fuyi
Lu, Jing
Liang, Feng
Zhang, Yiying
Xie, Zhongcong
Dong, Yuanlin
WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
title WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
title_full WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
title_fullStr WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
title_full_unstemmed WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
title_short WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
title_sort ws635 attenuates the anesthesia/surgery-induced cognitive impairment in mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335586/
https://www.ncbi.nlm.nih.gov/pubmed/34366827
http://dx.doi.org/10.3389/fnagi.2021.688587
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