Influence of hippocampal low-frequency stimulation on GABAA R α1, ICER and BNDF expression level in brain tissues of amygdala-kindled drug-resistant temporal lobe epileptic rats

Brain Res. 2018 Nov 1:1698:195-203. doi: 10.1016/j.brainres.2018.08.013. Epub 2018 Aug 15.

Abstract

This study investigated the therapeutic effect of hippocampal low-frequency stimulation (Hip-LFS) and its influence on the type A γ-aminobutyric acid receptor α1 subunit (GABAA R α1 subunit), inducible cAMP early repressor (ICER) and brain-derived neurotrophic factors (BNDF). The model of epilepsy was induced by chronic electrical stimulation in amygdala. Drug-resistant and drug-sensitive epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital. The changes of GABAA R α1 subunit, ICER and BDNF expression were detected via immunohistochemistry and western blot. The expression levels of ICER and BDNF were increased remarkably but the GABAA R α1 subunit decreased significantly in the drug-resistant epileptic rats. However, the expression levels of ICER, BDNF were decreased and the expression of the GABAA R α1 subunit increased significantly in the drug-resistant epileptic rats after two weeks of Hip-LFS. Meanwhile, the seizure degree was reduced and the electroencephalograms were improved. The present study demonstrated thatincreased ICER and BDNF might be associated with the development of drug-resistance. The effect of Hip-LFS in the treatment of drug-resistant epileptic rats might be associated with increasing the levels of the ICER and the BDNF.

Keywords: Brain-derived neurotrophic factors; Drug-resistant epilepsy; GABA(A) R α1 subunit; Hippocampal low-frequency stimulation; Inducible cAMP early repressor; Therapeutic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism*
  • Amygdala / physiopathology
  • Animals
  • Brain-Derived Neurotrophic Factor / biosynthesis*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cyclic AMP Response Element Modulator / biosynthesis*
  • Cyclic AMP Response Element Modulator / metabolism
  • Disease Models, Animal
  • Drug Resistant Epilepsy / metabolism
  • Drug Resistant Epilepsy / physiopathology
  • Electric Stimulation
  • Epilepsy, Temporal Lobe / metabolism*
  • Epilepsy, Temporal Lobe / physiopathology
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Kindling, Neurologic
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / biosynthesis*
  • Receptors, GABA-A / metabolism
  • Temporal Lobe / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Crem protein, rat
  • Gabra1 protein, rat
  • Receptors, GABA-A
  • Cyclic AMP Response Element Modulator
  • gamma-Aminobutyric Acid