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

Abstract

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, and Pak3) enriched in axon guidance also exhibited significant changes in the NAc after METH challenge injection. Moreover, expression levels of miR-204-3p, Sema3A and Plxna4 exhibited 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 of Sema3A and Plxna4. Our study provided a potential network of miR-204-3p-axon guidance in the NAc in the expression of METH-induced behavioral sensitization.