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Additionally, the expression levels of miR\u2010325\u20103p, miR\u2010326\u20103p, and miR\u2010330\u20105p, the predicted target miRNAs on TH, were significantly decreased. Based on these results, in this study, we investigated whether miRNA\u2010325\u20103p, miR\u2010326\u20103p, and miR\u2010330\u20105p modulate TH and manic\u2010like behaviors in SD rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Manic\u2010like behaviors were assessed using the open field test (OFT) and elevated plus\u2010maze (EPM) test. The direct binding activity of miRNAs to the 3\u2032\u2010untranslated region (3\u2032\u2010UTR) of the <jats:italic>Th<\/jats:italic> gene was measured in HEK\u2010293 cells using a luciferase reporter system. We also examined mRNA and protein expression of TH after intracerebroventricular (ICV) injection of miR\u2010330\u20105p agomir to SD rats, along with manic\u2010like behaviors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed an upregulation in mRNA and protein expression of TH and downregulation in miRNA\u2010325\u20103p, miR\u2010326\u20103p, and miR\u2010330\u20105p expressions in the prefrontal cortex of SD rats, together with increased manic\u2010like behaviors. The luciferase reporter assay showed that miR\u2010330\u20105p could repress TH expression through direct binding to its target site in the 3\u2032\u2010UTR of Th, whereas miR\u2010326\u20103p and miR\u2010330\u20105p could not. In addition, ICV injection of miR\u2010330\u20105p agomir alleviated the increase in TH expression in the prefrontal cortex of SD rats and manic\u2010like behaviors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TH expression regulation through miR\u2010330\u20105p may be implicated in the pathophysiology of mania in SD rats.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14121","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T09:19:45Z","timestamp":1676539185000},"page":"1525-1536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Downregulation of <scp>microRNA<\/scp>\u2010330\u20105p induces manic\u2010like behaviors in <scp>REM<\/scp> sleep\u2010deprived rats by enhancing tyrosine hydroxylase expression"],"prefix":"10.1111","volume":"29","author":[{"given":"Kang Hyun","family":"Leem","sequence":"first","affiliation":[{"name":"Department of Herbology, 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