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Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis

Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects o...

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Autores principales: Choi, Yunjung, Kim, Baeksun, Ham, Suji, Chung, Sooyoung, Maeng, Sungho, Kim, Hye-Sun, Im, Heh-In
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389495/
https://www.ncbi.nlm.nih.gov/pubmed/34437591
http://dx.doi.org/10.1371/journal.pone.0256390
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author Choi, Yunjung
Kim, Baeksun
Ham, Suji
Chung, Sooyoung
Maeng, Sungho
Kim, Hye-Sun
Im, Heh-In
author_facet Choi, Yunjung
Kim, Baeksun
Ham, Suji
Chung, Sooyoung
Maeng, Sungho
Kim, Hye-Sun
Im, Heh-In
author_sort Choi, Yunjung
collection PubMed
description Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects of acute subanesthetic ketamine treatment by bioinformatics analyses of miRNAs in the medial prefrontal cortex of male C57BL/6J mice. Gene Ontology and KEGG pathway analyses of the genes putatively targeted by ketamine-responsive prefrontal miRNAs revealed that acute subanesthetic ketamine modifies ubiquitin-mediated proteolysis. Validation analysis suggested that miR-148a-3p and miR-128-3p are the main players responsible for the subanesthetic ketamine-mediated alteration of ubiquitin-mediated proteolysis through varied regulation of ubiquitin ligases E2 and E3. Collectively, our data imply that the prefrontal miRNA-dependent modulation of ubiquitin-mediated proteolysis is at least partially involved in the mode of action by acute subanesthetic ketamine treatment.
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spelling pubmed-83894952021-08-27 Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis Choi, Yunjung Kim, Baeksun Ham, Suji Chung, Sooyoung Maeng, Sungho Kim, Hye-Sun Im, Heh-In PLoS One Research Article Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects of acute subanesthetic ketamine treatment by bioinformatics analyses of miRNAs in the medial prefrontal cortex of male C57BL/6J mice. Gene Ontology and KEGG pathway analyses of the genes putatively targeted by ketamine-responsive prefrontal miRNAs revealed that acute subanesthetic ketamine modifies ubiquitin-mediated proteolysis. Validation analysis suggested that miR-148a-3p and miR-128-3p are the main players responsible for the subanesthetic ketamine-mediated alteration of ubiquitin-mediated proteolysis through varied regulation of ubiquitin ligases E2 and E3. Collectively, our data imply that the prefrontal miRNA-dependent modulation of ubiquitin-mediated proteolysis is at least partially involved in the mode of action by acute subanesthetic ketamine treatment. Public Library of Science 2021-08-26 /pmc/articles/PMC8389495/ /pubmed/34437591 http://dx.doi.org/10.1371/journal.pone.0256390 Text en © 2021 Choi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Choi, Yunjung
Kim, Baeksun
Ham, Suji
Chung, Sooyoung
Maeng, Sungho
Kim, Hye-Sun
Im, Heh-In
Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
title Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
title_full Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
title_fullStr Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
title_full_unstemmed Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
title_short Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
title_sort subanesthetic ketamine rapidly alters medial prefrontal mirnas involved in ubiquitin-mediated proteolysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389495/
https://www.ncbi.nlm.nih.gov/pubmed/34437591
http://dx.doi.org/10.1371/journal.pone.0256390
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