Constitutive nuclear factor-κB activity is required for central neuron survival

Abstract

The function of nuclear factor (NF)-κB within the developing and mature CNS is controversial. We have generated transgenic mice to reveal NF-κB transcriptional activity in vivo. As expected, constitutive NF-κB activity was observed within immune organs, and tumor necrosis factor-inducible NF-κB activity was present in mesenchymal cells. Intriguingly, NF-κB activity was also prominent in the CNS throughout development, especially within neocortex, olfactory bulbs, amygdala, and hippocampus. NF-κB in the CNS was restricted to neurons and blocked by overexpression of dominant-negative NF-κB-inducible kinase or the IκBαM super repressor. Blocking endogenous neuronal NF-κB activity in cortical neurons using recombinant adenovirus induced neuronal death, whereas induction of NF-κB activity increased levels of anti-apoptotic proteins and was strongly neuroprotective. Together, these data demonstrate a physiological role for NF-κB in maintaining survival of central neurons.