The potential involvement of miR-204-3p-axon guidance network in methamphetamine-induced locomotor sensitization of mice

The potential involvement of miR-204-3p-axon guidance network in methamphetamine-induced locomotor sensitization of mice
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miR-204-3p-axon引导网络在甲基苯丙胺诱导的小鼠运动敏化中的潜在参与

DOI:
10.1016/j.neulet.2019.134303
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发表时间:
2019-08
影响因子:
2.5
通讯作者:
Teng Chen
Teng Chen
中科院分区:
医学4区
文献类型:
--
作者:
Tong Ni;Yanlin Li;Rui Wang;Tinghong Hu;Fanglin Guan;Li Zhu;Wei Han;Teng Chen

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MicroRNAs (miRNAs)是在药物成瘾中起重要作用的基因表达调控因子。我们之前报道了miR-204-3p是甲基苯丙胺(METH)致敏小鼠伏隔核(NAc)中唯一上调的miRNA。在这项研究中,我们报道了miR-204-3p在甲基安非他明致敏中的潜在机制。我们首先测量了甲基安非他明致敏小鼠NAc中miR-204-3p的表达变化。然后,我们利用生物信息学工具预测miR-204-3p的靶点,并将潜在靶点与ArrayExpress数据库中的meth应答基因相结合。通过KEGG通路分析探讨其潜在机制,并通过RT-PCR验证了4个富集基因。因此,miR-204-3p在NAc中从甲基甲氧基致敏的发育到表达呈现由下调到上调的转变。生物信息学分析预测了1834个可能的靶点,其中259个在甲基安非他明反应下在NAc中差异表达。这些靶点在轴突引导中显著富集(P= 9.59 × 10−6)。四种推测的轴突引导富集靶点(Sema3A、Plxna4、Rac1和pak3)在注射甲基甲氧基甲基后NAc也发生了显著变化。此外,miR-204-3p、sema3a和plxna4的表达水平与甲基安非他明致敏表达呈负相关。由此可见,miR-204-3p可能通过调节sema3aand plxna4的表达参与了甲基安非他明致敏的表达。我们的研究提供了mir -204-3p轴突在NAc中引导甲基甲醚诱导的行为致敏表达的潜在网络。
MicroRNAs (miRNAs) are gene expression regulators that play an important role in drug addiction. We previously reported miR-204-3p was the only up-regulated miRNA in the nucleus accumbens (NAc) in methamphetamine (METH)-sensitized mice. In this study, we are reporting a miR-204-3p potential mechanism in METH sensitization. We first measured the expression changes of miR-204-3p in the NAc of METH- sensitized mice. Then we predicted the targets of miR-204-3p by bioinformatics tools and combined the potential targets with the METH-responsive genes from the ArrayExpress database. KEGG pathway analyses were performed to investigate the prospective mechanisms and four enriched genes were validated by RT-PCR. As a result, miR-204-3p showed a shift from down-regulation to up-regulation in the NAc from the development to the expression of METH sensitization. Bioinformatics analysis predicted 1834 putative targets, 259 of which were differentially expressed in the NAc in response to METH. These targets were significantly enriched in axon guidance (P= 9.59 × 10−6). Four putative targets (Sema3A, Plxna4, Rac1, andPak3) enriched in axon guidance also exhibited significant changes in the NAc after METH challenge injection. Moreover, expression levels of miR-204-3p,Sema3AandPlxna4exhibited a negative association in the expression of METH sensitization. It appeared that miR-204-3p may be involved in the expression of METH sensitization by regulating the expression ofSema3AandPlxna4. Our study provided a potential network of miR-204-3p-axon guidance in the NAc in the expression of METH-induced behavioral sensitization.
DOI: 10.1016/j.neuropharm.2016.07.038
发表时间: 2016-11-01
期刊: NEUROPHARMACOLOGY
影响因子: 4.7
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