Choi, Yunjung Kim, Baeksun Ham, Suji Chung, Sooyoung Maeng, Sungho Kim, Hye-Sun Im, Heh-In 2024-01-19T14:02:58Z 2024-01-19T14:02:58Z 2022-01-10 2021-08 1932-6203 https://pubs.kist.re.kr/handle/201004/116629 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. English Public Library of Science Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis Article 10.1371/journal.pone.0256390 1 PLoS ONE, v.16, no.8 PLoS ONE 16 8 Y scie scopus 000697186000048 2-s2.0-85113748281 Multidisciplinary Sciences Science & Technology - Other Topics Article SYNAPTIC PLASTICITY PROTEASOME SYSTEM MAJOR DEPRESSION EXPRESSION GENE DEGRADATION MECHANISMS MIR-148A PATHWAY CONVERGENCE