Chronic methamphetamine regulates the expression of MicroRNAs and putative target genes in the nucleus accumbens of mice

J Neurosci Res. 2015 Oct;93(10):1600-10. doi: 10.1002/jnr.23605. Epub 2015 May 30.

Abstract

MicroRNAs (miRNAs) are modulators of gene expression that play key regulatory roles in distinct cellular processes. Methamphetamine (METH) induces various aberrant changes in the limbic system by affecting a complex gene regulatory mechanism, yet the involvement of miRNAs in the effects of METH exposure remains unclear. This study identifies METH-responsive miRNAs and their potential effects in the nucleus accumbens (NAc) of mice. Using miRNA sequencing, we examined the expression of miRNAs in the NAc of saline- and METH-treated mice and identified 45 known miRNAs to be METH responsive. Additionally, we identified two novel miRNA candidates that were METH responsive (novel-m002C and novel-m009C). Our target prediction analysis suggested that the known METH-regulated miRNAs might target genes that are involved in cellular autophagy, cellular metabolism, and immune responses and that the novel METH-regulated miRNA candidates might target genes that are related to drug addiction. We also matched the predicted targets of METH-regulated miRNAs with the NAc messenger RNA expression profile, revealing eight putative METH-regulated target genes (Arc, Capn9, Gbp5, Lefty1, Patl2, Pde4c, Strc, and Vmn1r58). Thus, METH triggers an alteration in NAc miRNA expression, which could contribute to METH-induced changes in neuron autophagy, metabolism, and immune responses. The differential expression of putative target genes suggests their involvement following exposure to METH.

Keywords: RNA-Seq; RRIDs; methamphetamine; microRNA; target genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Stimulants / pharmacology*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation / drug effects*
  • Genome / drug effects
  • Genome / genetics
  • Male
  • Methamphetamine / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Statistics, Nonparametric
  • Transcriptome

Substances

  • Central Nervous System Stimulants
  • Cytoskeletal Proteins
  • MicroRNAs
  • Nerve Tissue Proteins
  • RNA, Messenger
  • activity regulated cytoskeletal-associated protein
  • Methamphetamine