Cited by 75Epilepsy research and treatmentNF-κB Signaling PathwaysNeuroscience and Neuropharmacology Research

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

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Lubin, Farah D., Ren, Yajun, Xu, Xianghua, Anderson, Anne E.·2007·Journal of Neurochemistry

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.

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Crossref · 10.1111/j.1471-4159.2007.04863.x

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Authors
Lubin, F. D., Ren, Y., Xu, X., & Anderson, A. E.
Affiliations
Baylor College of Medicine (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2007-08-03
Volume
103
Issue
4
Pages
1381-1395
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2032443309
Cited by
75
References
80
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 9 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 7 · 2013: 8 · 2012: 3
FWCI
1.81
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (R01MH57014, R01MH057014)
  • National Institute of Neurological Disorders and Stroke (R01NS39942, F32NS048811)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
NF-κB signaling, status epilepticus, seizure susceptibility, kainate-induced seizures, IκBα, brain-derived neurotrophic factor, BDNF promoter, hippocampus, NF-κB inhibitors, transcriptional regulation
MeSH terms
Animals, Convulsants, Kainic Acid, Male, Seizures, Transcription, Genetic, Signal Transduction, NF-kappa B, Rats, Sprague-Dawley, Rats

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