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Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR

Ketamine is a widely used general anesthetic and has been reported to demonstrate neurotoxicity and neuroprotection. Investigation into the regulatory mechanism of ketamine on influencing neural development is of importance for a better and safer way of relieving pain. Reverse transcription-quantita...

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Autores principales: Zhou, Xuhui, Lv, Xiang, Zhang, Lei, Yan, Jia, Hu, Rong, Sun, Yu, Xi, Siwei, Jiang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185302/
https://www.ncbi.nlm.nih.gov/pubmed/32236601
http://dx.doi.org/10.3892/mmr.2020.11043
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author Zhou, Xuhui
Lv, Xiang
Zhang, Lei
Yan, Jia
Hu, Rong
Sun, Yu
Xi, Siwei
Jiang, Hong
author_facet Zhou, Xuhui
Lv, Xiang
Zhang, Lei
Yan, Jia
Hu, Rong
Sun, Yu
Xi, Siwei
Jiang, Hong
author_sort Zhou, Xuhui
collection PubMed
description Ketamine is a widely used general anesthetic and has been reported to demonstrate neurotoxicity and neuroprotection. Investigation into the regulatory mechanism of ketamine on influencing neural development is of importance for a better and safer way of relieving pain. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the critical neural associated gene expression, and flow cytometry to detect the neural differentiation effect. Hence, in the present study the underlying mechanism of ketamine (50 nM) on neural differentiation of the mouse embryonic stem cell (mESC) line 46C was investigated. The results demonstrated that a low dose of ketamine (50 nM) promoted the differentiation of mESCs to neural stem cells (NSCs) and activated mammalian target of rapamycin (mTOR) by upregulating the expression levels of phosphorylated (p)-mTOR. Furthermore, inhibition of the mTOR signaling pathway by rapamycin or knockdown of mTOR suppressed neural differentiation. A rescue experiment further confirmed that downregulation of mTOR inhibited the promotion of neural differentiation induced by ketamine. Taken together, the present study indicated that a low level of ketamine upregulated p-mTOR expression levels, promoting neural differentiation.
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spelling pubmed-71853022020-04-28 Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR Zhou, Xuhui Lv, Xiang Zhang, Lei Yan, Jia Hu, Rong Sun, Yu Xi, Siwei Jiang, Hong Mol Med Rep Articles Ketamine is a widely used general anesthetic and has been reported to demonstrate neurotoxicity and neuroprotection. Investigation into the regulatory mechanism of ketamine on influencing neural development is of importance for a better and safer way of relieving pain. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the critical neural associated gene expression, and flow cytometry to detect the neural differentiation effect. Hence, in the present study the underlying mechanism of ketamine (50 nM) on neural differentiation of the mouse embryonic stem cell (mESC) line 46C was investigated. The results demonstrated that a low dose of ketamine (50 nM) promoted the differentiation of mESCs to neural stem cells (NSCs) and activated mammalian target of rapamycin (mTOR) by upregulating the expression levels of phosphorylated (p)-mTOR. Furthermore, inhibition of the mTOR signaling pathway by rapamycin or knockdown of mTOR suppressed neural differentiation. A rescue experiment further confirmed that downregulation of mTOR inhibited the promotion of neural differentiation induced by ketamine. Taken together, the present study indicated that a low level of ketamine upregulated p-mTOR expression levels, promoting neural differentiation. D.A. Spandidos 2020-06 2020-03-30 /pmc/articles/PMC7185302/ /pubmed/32236601 http://dx.doi.org/10.3892/mmr.2020.11043 Text en Copyright: © Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhou, Xuhui
Lv, Xiang
Zhang, Lei
Yan, Jia
Hu, Rong
Sun, Yu
Xi, Siwei
Jiang, Hong
Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR
title Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR
title_full Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR
title_fullStr Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR
title_full_unstemmed Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR
title_short Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR
title_sort ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mtor
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185302/
https://www.ncbi.nlm.nih.gov/pubmed/32236601
http://dx.doi.org/10.3892/mmr.2020.11043
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