Constitutive nuclear factor-kappa B activity is required for central neuron survival.
The function of nuclear factor (NF)-kappaB within the developing and mature CNS is controversial. We have generated transgenic mice to reveal NF-kappaB transcriptional activity in vivo. As expected, constitutive NF-kappaB activity was observed within immune organs, and tumor necrosis factor-inducible NF-kappaB activity was present in mesenchymal cells. Intriguingly, NF-kappaB activity was also prominent in the CNS throughout development, especially within neocortex, olfactory bulbs, amygdala, and hippocampus. NF-kappaB in the CNS was restricted to neurons and blocked by overexpression of dominant-negative NF-kappaB-inducible kinase or the IkappaBalphaM super repressor. Blocking endogenous neuronal NF-kappaB activity in cortical neurons using recombinant adenovirus induced neuronal death, whereas induction of NF-kappaB activity increased levels of anti-apoptotic proteins and was strongly neuroprotective. Together, these data demonstrate a physiological role for NF-kappaB in maintaining survival of central neurons.
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D051034:Inhibitor of Apoptosis Proteins; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism; D051020:bcl-X Protein; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics; D000097782:NF-kappaB-Inducing Kinase
D049452:Green Fluorescent Proteins; D051034:Inhibitor of Apoptosis Proteins; D008164:Luminescent Proteins; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D014764:Viral Proteins; D051020:bcl-X Protein; D001616:beta-Galactosidase; D000097782:NF-kappaB-Inducing Kinase; C494812:Bcl2l1 protein, mouse; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus