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Nuclear factor‐κB regulates seizure threshold and gene transcription following convulsant stimulation
Author(s) -
Lubin Farah D.,
Ren Yajun,
Xu Xianghua,
Anderson Anne E.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04863.x
Subject(s) - status epilepticus , convulsant , transcription factor , chromatin immunoprecipitation , brain derived neurotrophic factor , biology , hippocampal formation , epilepsy , nfkb1 , neurotrophic factors , tropomyosin receptor kinase b , microbiology and biotechnology , neuroscience , gene , promoter , gene expression , genetics , receptor
Abstract 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.