Mir-181b Functions as Anti-Apoptotic Gene in Post-Status Epilepticus via Modulation of Nrarp and Notch Signaling Pathway

Ann Clin Lab Sci. 2015 Fall;45(5):550-5.

Abstract

Background: The expression pattern and function of miRs in the post-status epilepticus (SE) rat are still unclear. This study aimed to investigate the role and mechanism of miR-181b in the post- SE rat.

Methods: The lithium-pilocarpine-induced SE model was established in Sprague-Dawley rats. The expression of miR-181b in rat blood and hippocampus was confirmed by RT-PCR at 24 hous and 7 days post-SE. The expression of Nrarp, Hes-1, and Bcl-2 was detected by RT-PCR and western blot. After the rat model was treated with LV-rno-mir181b and LV-anti-181b-5p, the expression change of miR-181b, Nrarp, Hes-1, and Bcl-2 was examined again. The effects of altering the expression of miR-181b on neurone cell apoptosis post-SE were assessed.

Results: The expression of miR-181b significantly decreased both in post-SE rat hippocampus and peripheral blood at 24 hours and 7 days (p<0.05). Nrarp is up-regulated, however, Hes-1 and Bcl-2 are down-regulated (p<0.05). LV-miR-181b treatment induced down-regulation of Nrarp and up-regulation of Hes-1 and Bcl-2 (p<0.05). Neurone cell apoptosis decreased in miR-181b group and post-SE rat hippocampal (p<0.05).

Conclusions: Our study showed the low-expression of miR-181b in the hippocampus in a post-SE rat model. MiR-181b negatively regulated Nrarp as an anti-apoptotic gene via Notch signaling pathway.

Keywords: Apoptosis; Hippocampus; MiRNA; Status epilepticus.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hippocampus / pathology
  • Hippocampus / physiology*
  • Male
  • MicroRNAs / genetics*
  • Neurons / pathology
  • Neurons / physiology
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Sprague-Dawley
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction / genetics
  • Status Epilepticus / genetics*
  • Status Epilepticus / metabolism
  • Status Epilepticus / pathology

Substances

  • MIRN181 microRNA, rat
  • MicroRNAs
  • Nrarp protein, rat
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Notch