Constitutive nuclear factor-kappa B activity is required for central neuron survival

J Neurosci. 2002 Oct 1;22(19):8466-75. doi: 10.1523/JNEUROSCI.22-19-08466.2002.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • 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
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • 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
  • bcl-X Protein
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics

Substances

  • Bcl2l1 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Luminescent Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factor RelA
  • Viral Proteins
  • bcl-X Protein
  • inhibitor of apoptosis, Nucleopolyhedrovirus
  • Green Fluorescent Proteins
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase
  • beta-Galactosidase