microRNA-Seq reveals cocaine-regulated expression of striatal microRNAs

  1. Brenton R. Graveley1,4
  1. 1Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
  2. 2Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
    • 3 Present address: Institute for Stem Cell Biology and Regenerative Medicine (inStem), National Centre for Biological Sciences, GKVK Campus, Bangalore 560069, India.

    Abstract

    MicroRNAs (miRNAs) are small RNAs that modulate gene expression by binding target mRNAs. The hundreds of miRNAs expressed in the brain are critical for synaptic development and plasticity. Drugs of abuse cause lasting changes in the limbic regions of the brain that process reward, and addiction is viewed as a form of aberrant neuroplasticity. Using next-generation sequencing, we cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes. The miR-8 family, known for its roles in cancer, is highly enriched and cocaine regulated at striatal synapses, where its members may affect expression of cell adhesion molecules. Synaptically enriched cocaine-regulated miRNAs may contribute to long-lasting drug-induced plasticity through fine-tuning regulatory pathways that modulate the actin cytoskeleton, neurotransmitter metabolism, and peptide hormone processing.

    Keywords

    Footnotes

    • Received April 11, 2011.
    • Accepted May 6, 2011.
    | Table of Contents