RGD Reference Report - Nuclear factor-kappa B regulates seizure threshold and gene transcription following convulsant stimulation. - Rat Genome Database

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

Authors: Lubin, FD  Ren, Y  Xu, X  Anderson, AE 
Citation: Lubin FD, etal., J Neurochem. 2007 Nov;103(4):1381-95. Epub 2007 Aug 28.
RGD ID: 2298852
Pubmed: PMID:17727632   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2007.04863.x   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
status epilepticus  ISORela (Rattus norvegicus)2298852; 2298852protein:increased expression:nucleus and hippocampusRGD 
status epilepticus  IDA 2298852protein:increased expression:nucleus and hippocampusRGD 

Objects Annotated

Genes (Rattus norvegicus)
Rela  (RELA proto-oncogene, NF-kB subunit)

Genes (Mus musculus)
Rela  (v-rel reticuloendotheliosis viral oncogene homolog A (avian))

Genes (Homo sapiens)
RELA  (RELA proto-oncogene, NF-kB subunit)


Additional Information