Observations on the function of nuclear factor kappa B (NF-kappaB) in the survival of adult primary sensory neurons after nerve injury.
Peripheral nerve transections cause much more neuronal death in embryonic and neonatal dorsal root ganglia (DRG) than in adult DRG. Here we used transgenic approaches to examine the hypothesis that NF-kappaB is an important intrinsic factor of adult DRG neurons for their in vivo capacity to survive after nerve injury. We generated transgenic mice expressing the NF-kappaB super-inhibitor (IkappaBalpha-SI), a multi-mutant form of IkappaBalpha, specifically in adult neurons. Adult DRG neurons in these transgenic animals are not abnormally susceptible to apoptosis after peripheral nerve injury, although there is a significant inhibition in the ability of NF-kappaB to translocate into their nucleus. We investigated the observed lack of NF-kappaB neuroprotective function at the level of NF-kappaB transcriptional activity using transgenic NF-kappaB/LacZ reporter mice. We show that the expression of the NF-kappaB reporter transgene is restricted in naïve and injured DRG neurons. However, NF-kappaB transcriptional activity in adult DRG neurons is evident upon exposure to Trichostatin A (TSA) which is a specific inhibitor of histone deacetylases. Taken together our results illustrate that the functions of NF-kappaB are limited in adult primary sensory neurons due to a transcriptional repression mechanism mediated by histone deacetylases, and that intrinsic neuroprotective factors other than NF-kappaB are responsible for the resistance of adult DRG neurons to apoptosis in response to nerve injury.
Gushchina
Svetlana
S
Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, 4 Newark Street, Whitechapel, London E12AT, UK.
Leinster
Veronica
V
Wu
Dongsheng
D
Jasim
Avin
A
Demestre
Maria
M
Lopez de Heredia
Luis
L
Michael
Gregory J
GJ
Barker
Philip A
PA
Richardson
Peter M
PM
Magoulas
Charalambos
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019771:Axotomy; D002470:Cell Survival; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology* / Q000502:physiology; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000473:pathology* / Q000502:physiology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha