Acute Ethanol Administration Increases Mir-124 Expression via Histone Acetylation in the BrainKeisuke Mizuo*, Shunichiro Okazaki, Satoshi Watanabe, Hiromasa Inoue and Hiroshi Matsumoto
Department of Legal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Corresponding Author:
- Keisuke Mizuo
Department of Legal Medicine and Molecular Alcohology,
Sapporo Medical University School of Medicine,
S-1 W-17, Chuo-ku, Sapporo 060-8556, Japan
E-mail: [email protected]
Received date: January 28, 2016 Accepted date: February 29, 2016 Published date: March 04, 2016
Citation: Mizuo K, Okazaki S, Watanabe S, Inoue H, Matsumoto H (2016) Acute Ethanol Administration Increases Mir-124 Expression via Histone Acetylation in the Brain. J Alcohol Drug Depend 4:232. doi: 10.4172/2329-6488.1000232
Copyright: © 2016 Mizuo K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute ethanol administration causes an enhancement of mesolimbic dopaminergic activity in the brain. The microRNAs miR-124 and miR-132 are highly expressed in the central nervous system and contribute to the regulation of mesolimbic dopaminergic activity. However, the nature of a potential mechanistic association between ethanol and these microRNAs has remained unclear. Recent studies reported that the expression of some microRNAs was regulated by histone acetylation. In this study, we investigated whether ethanol administration can change the expression of miR-124 and miR-132 via histone acetylation in mouse brain. We administered 2 g/kg ethanol (s.c.) to male C57BL / 6J mice. Total RNA was extracted using TRIzol in the whole brain 1 to 12 hr after administration. MicroRNAs were detected by northern blotting. Acetylated histone H3 and histone deacetylases (HDACs) were detected by western blotting analysis and immunohistochemistry. Trichostatin A (TSA) was administered intracerebroventricularly.
Acute ethanol administration increased expression of miR-124 and miR-132 in the mouse whole brain 12 hr after ethanol administration. Acute ethanol administration significantly increased acetylated histone H3 in the nuclear fraction of mouse whole brain, especially the nucleus accumbens and ventral tegmental area. HDAC4 expression was significantly decreased in the nuclear fraction after acute ethanol administration. These findings suggest that acute administration induces histone acetylation by reducing nuclear HDAC4 expression. TSA treatment increased the expression of miR-124 in mouse whole brain. These findings suggest that HDAC4 may directly regulate the expression of miR-124 in the brain. In conclusion, acute ethanol administration induces histone acetylation via reducing nuclear HDAC4 protein, resulting in increased microRNA expression in the brain.