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PMID: 12351721 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 19 ·2002-10-01 ·Pages 8466-75

Bhakar AL, Tannis LL, Zeindler C, Russo MP, Jobin C, Park DS, MacPherson S, Barker PA

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.

MeSH Terms
Animals Cell Survival/physiology Cells, Cultured Central Nervous System/cytology,metabolism Fibroblasts/cytology Genes, Reporter Green Fluorescent Proteins Inhibitor of Apoptosis Proteins Kidney/cytology,metabolism Luminescent Proteins/biosynthesis,genetics Mice Mice, Transgenic NF-kappa B/biosynthesis,genetics,metabolism Neurons/cytology,metabolism Organ Specificity Protein Serine-Threonine Kinases/genetics,metabolism Proto-Oncogene Proteins c-bcl-2/metabolism Signal Transduction/physiology Transcription Factor RelA Transfection Viral Proteins/metabolism bcl-X Protein beta-Galactosidase/biosynthesis,genetics
Chemicals
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
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bhakar Asha L
Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4. phil.barker@mcgill.ca
Tannis Laura-Lee
Zeindler Christine
Russo Maria Pia
Jobin Christian
Park David S
MacPherson Sandra
Barker Philip A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
phil.barker@mcgill.ca
Published
2002-10-01
Pages
8466-75
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6757785
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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