Decreased GABABR expression and increased neuronal cell death in developing rat brain after PTZ-induced seizure

Neurol Sci. 2013 Apr;34(4):497-503. doi: 10.1007/s10072-012-1083-0. Epub 2012 Apr 7.

Abstract

The objective of this study was to evaluate the PTZ-induced seizures effects on GABAB receptor (R) expression and to observe its neurodegenerative effect in hippocampal part of developing rat brain. In the present study, high dose of pentylenetetrazol (PTZ 40 mg/kg) was injected in developing rats of age 5 weeks having average weight of 60-65 g for 4 days. Further, baclofen (B 3 mg/kg i.p) agonist and phaclofen (P 30 μg/rat) antagonist of GABABR were injected along with PTZ. Western blot analysis was used to elucidate expression of GABABR protein upon PTZ, baclofen and phaclofen exposure in the developing rat brain. Furthermore, PTZ-induced apoptotic neurodegeneration was also observed through the release of caspase-3 antibody and propidium iodide (PI) staining using confocal microscopy. Seizure was confirmed using electroencephalography (EEG) data obtained from the Laxtha EEG-monitoring device in the EEG recording room and EEG was monitored 5-15 min after PTZ injection. The results of the present study showed that PTZ-induced seizure significantly decreased GABABR expression and induced neuronal apoptosis in cortical and hippocampal part of brain. While, baclofen reverse the effect of PTZ by increasing the expression of GABABR as compared to the PTZ- , PTZ plus B- and PTZ plus P-treated groups. Our findings indicated that PTZ-induced seizure showed not only decrease in GABABR expression but also cause neuronal apoptosis in the developing rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Baclofen / analogs & derivatives
  • Baclofen / pharmacology
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Disease Models, Animal
  • Electroencephalography
  • GABA Antagonists / toxicity*
  • GABA-B Receptor Agonists / pharmacology
  • Gene Expression Regulation, Developmental / drug effects*
  • Hippocampus* / drug effects
  • Hippocampus* / growth & development
  • Hippocampus* / metabolism
  • Microscopy, Confocal
  • Neurons / drug effects
  • Pentylenetetrazole / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / metabolism*
  • Seizures / chemically induced
  • Seizures / pathology*

Substances

  • GABA Antagonists
  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • phaclofen
  • Caspase 3
  • Baclofen
  • Pentylenetetrazole