Molecular expression and functional analysis of genes in children with temporal lobe epilepsy

J Integr Neurosci. 2019 Mar 30;18(1):71-77. doi: 10.31083/j.jin.2019.01.13.

Abstract

Temporal lobe epilepsy is the most common form of epilepsy. However, for this type of condition, antiseizure medication is not effective for children. As miRNAs are involved in the development of temporal lobe epilepsy in children, they may provide potential therapeutic approaches for treatment. The primary aim of this study was to explore the expression and function of miR-135a-5p in children with temporal lobe epilepsy. Hippocampal slices from either normal (control) children or children with temporal lobe epilepsy were used to detect the expression of miR-135a-5p and its target gene caspase activity and apoptosis inhibitor 1. To further explore the role of miR-135a-5p in the development of temporal lobe epilepsy in children, primary hippocampal neurons from newborn rats were cultured in vitro in a magnesium-free medium to mimic the temporal lobe epilepsy condition in children. The effect of transfection of miR-135a-5p inhibitor into cells was also assessed. Apoptosis and proliferation of hippocampus cells was respectively assessed by flow cytometry or 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The level of miR-135a-5p was significantly increased in both children with temporal lobe epilepsy and the epileptiform discharge model that employed newborn rat hippocampal neurons; whereas, the expression of caspase activity and apoptosis inhibitor 1 was downregulated by overexpression of miR-135a-5p. Moreover, miR-135a-5p mediated the pro-apoptotic effect of temporal lobe epilepsy via repressing caspase activity and apoptosis inhibitor 1 expression. Additionally, miR-135a-5p reduced cell survival in the temporal lobe epilepsy condition. Overexpression of miR-135a-5p induced cell apoptosis through inhibition of caspase activity and apoptosis inhibitor 1 expression and suppressed cell survival in children with temporal lobe epilepsy.

Keywords: CAAP1; functional analysis; miR-135a-5p; temporal lobe epilepsy.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Survival / physiology
  • Cells, Cultured
  • Child
  • Epilepsy, Temporal Lobe / metabolism*
  • Female
  • Hippocampus / metabolism
  • Humans
  • Male
  • MicroRNAs / metabolism
  • Primary Cell Culture
  • Rats, Wistar

Substances

  • Apoptosis Regulatory Proteins
  • CAAP1 protein, human
  • MIRN135 microRNA, human
  • MIRN135 microRNA, rat
  • MicroRNAs