NF-κB p50 is increased in neurons surviving hippocampal injury

K. R. Pennypacker, C. A. Kassed, S. Eidizadeh, S. Saporta, P. R. Sanberg, A. E. Willing

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Signal transduction pathways that lead to the modulation of genes related to survival and repair mechanisms are activated in neurons that survive injury. These protein kinase/phosphatase cascades converge on transcription factors, the DNA binding proteins that directly regulate gene expression. In this study we examined expression of the NF-κB p50 subunit in the rat hippocampus 7 days after injury caused by middle cerebral artery occlusion or trimethyltin treatment. We found increased levels of p50 in neurons throughout the hippocampus after both treatments, localized not only in cell bodies but also in processes. At the 7-day time point, Fluoro-Jade histochemistry revealed hippocampal neurodegeneration in trimethyltin-treated rats but not in those lesioned by middle cerebral artery occlusion. p50 was not expressed in Fluoro-Jade-positive degenerating cells, supporting the role of this transcriptional subunit in neurosurvival. Because phosphorylation of the inhibitor IκB protein by IκB kinase is the classic step in NF-κB activation, phospho-IκBα immunoreactivity was examined as an indication of IκB kinase activity. Levels of phospho-IκBα were increased in neurons throughout the hippocampus 7 days postinjury. Immunoblotting for phospho-IκBα demonstrated increased levels 1 day postinjury that remained elevated for at least 7 days. These data suggest that NF-κB signal transduction is involved in an adaptive response of neurons that survive injury.

Original languageEnglish
Pages (from-to)307-319
Number of pages13
JournalExperimental Neurology
Issue number2
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by grants from American Heart Association National, 9930072N, and National Institutes of Health, NS39141-01A2.


  • Fluoro-Jade
  • Ischemia
  • IκB kinase
  • Neurodegeneration
  • Signal transduction pathway
  • Transcription factor

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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