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:	Yunjung Choi, Baeksun Kim, Suji Ham, Sooyoung Chung, Sungho Maeng, Hye-Sun Kim, Heh-In Im
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aad8d89e18614e7ba6b6ef07dc77fd95
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spelling	oai:doaj.org-article:aad8d89e18614e7ba6b6ef07dc77fd952021-12-02T20:19:32ZSubanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis.1932-620310.1371/journal.pone.0256390https://doaj.org/article/aad8d89e18614e7ba6b6ef07dc77fd952021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256390https://doaj.org/toc/1932-6203Ketamine 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.Yunjung ChoiBaeksun KimSuji HamSooyoung ChungSungho MaengHye-Sun KimHeh-In ImPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256390 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yunjung Choi Baeksun Kim Suji Ham Sooyoung Chung Sungho Maeng Hye-Sun Kim Heh-In Im Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis.
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.
format	article
author	Yunjung Choi Baeksun Kim Suji Ham Sooyoung Chung Sungho Maeng Hye-Sun Kim Heh-In Im
author_facet	Yunjung Choi Baeksun Kim Suji Ham Sooyoung Chung Sungho Maeng Hye-Sun Kim Heh-In Im
author_sort	Yunjung Choi
title	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_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_sort	subanesthetic ketamine rapidly alters medial prefrontal mirnas involved in ubiquitin-mediated proteolysis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/aad8d89e18614e7ba6b6ef07dc77fd95
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Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis.

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