Downregulation of microRNA-330-5p induces manic-like behaviors in REM sleep-deprived rats by enhancing tyrosine hydroxylase expression |
| |
Authors: | Kang Hyun Leem Sanga Kim Hee Won Kim Hae Jeong Park |
| |
Institution: | 1. Department of Herbology, College of Korean Medicine, Semyung University, Jecheon, Korea;2. Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Korea;3. Department of Medical Engineering, Graduate School, Kyung Hee University, Seoul, Korea |
| |
Abstract: | Aim In our pilot study, we found an increase in tyrosine hydroxylase (Th) mRNA expression in the prefrontal cortex of 72-h REM sleep-deprived (SD) rats, a mania model. Additionally, the expression levels of miR-325-3p, miR-326-3p, and miR-330-5p, the predicted target miRNAs on TH, were significantly decreased. Based on these results, in this study, we investigated whether miRNA-325-3p, miR-326-3p, and miR-330-5p modulate TH and manic-like behaviors in SD rats. Methods Manic-like behaviors were assessed using the open field test (OFT) and elevated plus-maze (EPM) test. The direct binding activity of miRNAs to the 3′-untranslated region (3′-UTR) of the Th gene was measured in HEK-293 cells using a luciferase reporter system. We also examined mRNA and protein expression of TH after intracerebroventricular (ICV) injection of miR-330-5p agomir to SD rats, along with manic-like behaviors. Results We observed an upregulation in mRNA and protein expression of TH and downregulation in miRNA-325-3p, miR-326-3p, and miR-330-5p expressions in the prefrontal cortex of SD rats, together with increased manic-like behaviors. The luciferase reporter assay showed that miR-330-5p could repress TH expression through direct binding to its target site in the 3′-UTR of Th, whereas miR-326-3p and miR-330-5p could not. In addition, ICV injection of miR-330-5p agomir alleviated the increase in TH expression in the prefrontal cortex of SD rats and manic-like behaviors. Conclusions TH expression regulation through miR-330-5p may be implicated in the pathophysiology of mania in SD rats. |
| |
Keywords: | manic-like behavior miR-330-5p prefrontal cortex rapid eye movement sleep deprivation tyrosine hydroxylase |
|
|