Pilocarpine-induced seizures trigger differential regulation of microRNA-stability related genes in rat hippocampal neurons

Sci Rep. 2016 Feb 12;6:20969. doi: 10.1038/srep20969.

Abstract

Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application promptly (<30 min) induces status epilepticus (SE) as revealed by changes in rat electrocorticogram particularly in fast-beta range (21-30 Hz). SE simultaneously upregulated XRN2 and downregulated PAPD4 gene expression in the hippocampus, two genes related to miRNA degradation and stability, respectively. Moreover, SE decreased the number of XRN2-positive cells in the hilus, while reduced the number of PAPD4-positive cells in CA1. XRN2 and PAPD4 levels did not change in calretinin- and CamKII-positive cells, although it was possible to determine that PAPD4, but not XRN2, was upregulated in parvalbumin-positive cells, revealing that SE induction unbalances the accumulation of these functional-opposed proteins in inhibitory interneurons that directly innervate distinct domains of pyramidal cells. Therefore, we were able to disclose a possible mechanism underlying the differential regulation of miRNAs in specific neurons during epileptogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • GABAergic Neurons / metabolism
  • Gene Expression Regulation
  • Hippocampus / pathology*
  • Interneurons / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neurons / metabolism*
  • Organ Specificity / genetics
  • Parvalbumins / metabolism
  • Pilocarpine
  • RNA Stability / genetics*
  • Rats, Wistar
  • Seizures / chemically induced*
  • Seizures / genetics*
  • Seizures / pathology
  • Status Epilepticus / chemically induced
  • Status Epilepticus / genetics
  • Status Epilepticus / pathology
  • Subcellular Fractions / metabolism
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • MicroRNAs
  • Parvalbumins
  • mRNA Cleavage and Polyadenylation Factors
  • Pilocarpine
  • 5'-3' exoribonuclease 2, rat
  • Exoribonucleases