MicroRNA expression profile and functional analysis reveal that miR-382 is a critical novel gene of alcohol addiction

MicroRNA 表达谱和功能分析表明 miR-382 是酒精成瘾的一个关键新基因

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作者:Jingyuan Li, Jing Li, Xiaojun Liu, Shanshan Qin, Yanzhong Guan, Yuwei Liu, Yunhui Cheng, Xiuwen Chen, Wen Li, Shenming Wang, Ming Xiong, Eldo V Kuzhikandathil, Jiang-Hong Ye, Chunxiang Zhang

Abstract

Alcohol addiction is a major social and health concern. Here, we determined the expression profile of microRNAs (miRNAs) in the nucleus accumbens (NAc) of rats treated with alcohol. The results suggest that multiple miRNAs were aberrantly expressed in rat NAc after alcohol injection. Among them, miR-382 was down-regulated in alcohol-treated rats. In both cultured neuronal cells in vitro and in the NAc in vivo, we identified that the dopamine receptor D1 (Drd1) is a direct target gene of miR-382. Via this target gene, miR-382 strongly modulated the expression of DeltaFosB. Moreover, overexpression of miR-382 significantly attenuated alcohol-induced up-regulation of DRD1 and DeltaFosB, decreased voluntary intake of and preference for alcohol and inhibited the DRD1-induced action potential responses. The results indicated that miRNAs are involved in and may represent novel therapeutic targets for alcoholism.

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