Nuclear factor‐κB regulates seizure threshold and gene transcription following convulsant stimulation
Open accessAbstract
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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BDNF is overexpressed at the onset of seizures.
“As BDNF is overexpressed at the onset of seizures [194]”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [194]
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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
- bronze
- doi.org
- 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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