Constitutive Nuclear Factor-kappa B Activity Is Required for Central Neuron Survival

• Published in: The Journal of neuroscience Vol. 22; no. 19; pp. 8466 - 8475
• Main Authors: Bhakar, Asha L, Tannis, Laura-Lee, Zeindler, Christine, Russo, Maria Pia, Jobin, Christian, Park, David S, MacPherson, Sandra, Barker, Philip A
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.10.2002; Society for Neuroscience
• Subjects: Animals; bcl-X Protein; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Cell Survival - physiology; Cells, Cultured; Central Nervous System - cytology; Central Nervous System - metabolism; Fibroblasts - cytology; Genes, Reporter; Green Fluorescent Proteins; Inhibitor of Apoptosis Proteins; Kidney - cytology; Kidney - metabolism; Luminescent Proteins - biosynthesis; Luminescent Proteins - genetics; Mice; Mice, Transgenic; Neurons - cytology; Neurons - metabolism; NF-kappa B - biosynthesis; NF-kappa B - genetics; NF-kappa B - metabolism; NF-kappaB-Inducing Kinase; Organ Specificity; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal Transduction - physiology; Transcription Factor RelA; Transfection; Viral Proteins - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.22-19-08466.2002

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.