Lack of NF-κB p50 exacerbates degeneration of hippocampal neurons after chemical exposure and impairs learning

C. A. Kassed, A. E. Willing, S. Garbuzova-Davis, P. R. Sanberg, K. R. Pennypacker

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


The roles of activated NF-κB subunits in the CNS remain to be discerned. Members of this family of transcription factors are essential to diverse physiological processes and can be activated by pathogens, stress, pharmacological agents, and trauma. We are particularly interested in long-term NF-κB activation and its involvement in neuroplastic changes in the brain resulting from acquisition of memory as well as injury. Here, we use lesioning by the limbic-specific neurotoxicant trimethyltin (TMT) as a model in which to examine activation of the NF-κB p50 subunit before, during, and after neuronal degeneration. Neurons in wild-type mice that survived TMT-induced injury contained activated p50 and did not label with Fluoro-Jade, a histochemical marker of degenerating neurons. Granule cells of the wild-type dentate gyrus subregion, an area particularly vulnerable to TMT-induced degeneration, contained less activated p50 protein than CA regions. We compared the extent of degeneration in wild-type and p50-null mice and found a fivefold increase in death of hippocampal neurons in mice lacking p50. The hippocampus is key to processes of learning and memory, and NF-κB has reported involvement in these processes. The enhanced hippocampal degeneration in p50-null mice prompted us to evaluate their basal learning abilities, and we discovered that difficulties in task acquisition were an additional consequence of p50 ablation. These results indicate that absence of p50 negatively modulates learning ability as well as hippocampal responsiveness to brain injury after a chemical-induced lesion.

Original languageEnglish
Pages (from-to)277-288
Number of pages12
JournalExperimental Neurology
Issue number2
StatePublished - 2002

Bibliographical note

Funding Information:
Supported by NIH Grant RO1 NS39141-01A2 and American Heart Association Grant 9930072N.


  • Hippocampus
  • Knockout mice
  • Learning and memory
  • NF-κB
  • Neurodegeneration
  • Neuroplasticity
  • Neuroprotection
  • Signal transduction
  • Transcription factors
  • Trimethyltin

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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