The inhibitor of IkappaBalpha phosphorylation BAY 11-7082 prevents NMDA neurotoxicity in mouse hippocampal slices

NF-κB is a nuclear transcription factor involved in the control of fundamental cellular functions including cell survival. Among the many target genes of this factor, both pro- and anti-apoptotic genes have been described. To evaluate the contribution of NF-κB activation to excitotoxic insult, we analysed the effect of IkappaBalpha (IκBα) phosphorylation blockade on glutamate-induced toxicity in adult mouse hippocampal slices. By using immunocytochemical and EMSA techniques, we found that (i) acute exposure of hippocampal slices to NMDA induced nuclear translocation of NF-κB, (ii) NMDA-mediated activation of NF-κB was prevented by BAY 11-7082, an inhibitor of IκBα phosphorylation and degradation, and (iii) BAY 11-7082-mediated inhibition of NF-κB activation was associated with neuroprotection.