Ago2 and Dicer1 are involved in METH-induced locomotor sensitization in mice via biogenesis of miRNA
Ago2 and Dicer1 are involved in METH-induced locomotor sensitization in mice via biogenesis of miRNA
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Ago2 和 Dicer1 通过 miRNA 的生物发生参与 METH 诱导的小鼠运动敏化
DOI：
10.1111/adb.12616
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Chen, Teng
中科院分区：
文献类型：
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作者：
Liu, Dan;Zhu, Li;Chen, Teng
microRNA（miRNA）在药物成瘾中起重要作用，是基因表达的转录后调节因子。我们先前报道了甲基苯丙胺（METH）致敏小鼠的延髓核（NAc）中miRNA的广泛下调。然而，这种MET诱导的miRNAs下调的调控机制尚未阐明。因此，我们研究了在METH诱导的运动致敏小鼠的延髓核中，METH诱导的miRNA及其前体表达的变化，以及mRNA和参与miRNA生物合成的蛋白质（如Dicer 1和Ago 2）的表达水平。miRNA和Ago 2的表达显著下调，而miRNA前体的表达保持不变或上调，这表明miRNA的下调可能是由于Ago 2介导的剪接减少，但不太可能在转录水平上受到调控。有趣的是，Dicer 1的表达水平显著增加，Dicer 1是METH诱导的减少的miRNA（如miR-124、miR-212和miR-29 b）的潜在靶点。总之，这项研究表明，miRNA生物合成（如Ago 2和Dicer 1）及其miRNA产物可能在METH成瘾的发展中发挥作用。
microRNA (miRNA) play important roles in drug addiction and act as a post-transcriptional regulator of gene expression. We previously reported extensive downregulation of miRNAs in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice. However, the regulatory mechanism of this METH-induced downregulation of miRNAs has yet to be elucidated. Thus, we examined METH-induced changes in the expression of miRNAs and their precursors, as well as the expression levels of mRNA and the proteins involved in miRNA biogenesis such as Dicer1 and Ago2, in the nucleus accumbens of METH-induced locomotor sensitized mice. miRNAs and Ago2 were significantly downregulated, while the expression of miRNA precursors remained unchanged or upregulated, which suggests that the downregulation of miRNAs was likely due to a reduction in Ago2-mediated splicing but unlikely to be regulated at the transcription level. Interestingly, the expression level of Dicer1, which is a potential target of METH-induced decreased miRNAs, such as miR-124, miR-212 and miR-29b, was significantly increased. In conclusion, this study indicates that miRNA biogenesis (such as Ago2 and Dicer1) and their miRNA products may have a role in the development of METH addiction.