Nuclear factor-κB regulates seizure threshold and gene transcription following convulsant stimulation.

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