Nuclear factor-kappa B regulates seizure threshold and gene transcription following convulsant stimulation

J Neurochem. 2007 Nov;103(4):1381-95. doi: 10.1111/j.1471-4159.2007.04863.x. Epub 2007 Aug 28.


We evaluated a role for the nuclear factor-kappa B (NF-kappaB) pathway in the regulation of seizure susceptibility and transcriptional activation during prolonged, continuous seizures (status epilepticus). Using two functionally distinct NF-kappaB inhibitors we observed a decrease in latency to onset of kainate-induced seizures and status epilepticus. To assess NF-kappaB transcriptional activation, we evaluated inhibitor kappa B alpha (IkappaBalpha) and brain-derived neurotrophic factor (bdnf) gene targets. Inhibition of the NF-kappaB signaling pathway significantly attenuated the increases in IkappaBalpha and bdnf mRNA levels that occurred during prolonged seizure activity, suggesting that the NF-kappaB pathway was involved in the up-regulation of these transcripts during status epilepticus. DNA-binding studies and chromatin immunoprecipitation assays using hippocampal extracts from animals with status epilepticus revealed that NF-kappaB subunits were associated with the candidate kappaB-binding elements within promoter 1 of the bdnf gene. The pattern of association was different for the p50 and p65 subunits supporting complex NF-kappaB modifications within promoter 1. In summary, our findings provide additional insights into the role of NF-kappaB transcriptional regulation in hippocampus following status epilepticus and suggest that NF-kappaB pathway activation contributes to seizure susceptibility.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Convulsants / toxicity*
  • Kainic Acid / toxicity
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / biosynthesis
  • NF-kappa B / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / genetics
  • Seizures / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology*


  • Convulsants
  • NF-kappa B
  • Kainic Acid