PMID- 17727632
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20220311
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 103
IP  - 4
DP  - 2007 Nov
TI  - Nuclear factor-kappa B regulates seizure threshold and gene transcription 
      following convulsant stimulation.
PG  - 1381-95
AB  - 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.
FAU - Lubin, Farah D
AU  - Lubin FD
AD  - Cain Foundation Laboratories, Department of Pediatrics, Baylor College of 
      Medicine, Houston, Texas, USA, and Department of Neuroscience, Baylor College of 
      Medicine, Houston, Texas, USA.
FAU - Ren, Yajun
AU  - Ren Y
FAU - Xu, Xianghua
AU  - Xu X
FAU - Anderson, Anne E
AU  - Anderson AE
LA  - eng
GR  - F32NS048811/NS/NINDS NIH HHS/United States
GR  - R01MH57014/MH/NIMH NIH HHS/United States
GR  - R01NS39942/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070828
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Convulsants)
RN  - 0 (NF-kappa B)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Convulsants/*toxicity
MH  - Kainic Acid/toxicity
MH  - Male
MH  - NF-kappa B/antagonists & inhibitors/biosynthesis/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seizures/chemically induced/genetics/*metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - Transcription, Genetic/drug effects/*physiology
EDAT- 2007/08/31 09:00
MHDA- 2007/12/14 09:00
CRDT- 2007/08/31 09:00
PHST- 2007/08/31 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/08/31 09:00 [entrez]
AID - JNC4863 [pii]
AID - 10.1111/j.1471-4159.2007.04863.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Nov;103(4):1381-95. doi: 10.1111/j.1471-4159.2007.04863.x. Epub 
      2007 Aug 28.