G. Taglialatela et al., CENTRAL-NERVOUS-SYSTEM DNA FRAGMENTATION INDUCED BY THE INHIBITION OFNUCLEAR FACTOR-KAPPA-B, NeuroReport, 9(3), 1998, pp. 489-493
AGEING of the central nervous system (CNS) is characterized by a progr
essive apoptotic loss of neurons that may be in part due to impaired n
eurotrophin signaling mediated by such elements as the transcription f
actor nuclear factor kappa B (NF kappa B). To support this hypothesis,
we inhibited nuclear translocation of NF kappa B in vivo by injecting
a proteasome inhibitor (PSI) directly in tile CNS lateral ventricle o
f rats and then measured fragmented DNA in various CNS areas as an ind
ex of ongoing apoptosis. Our results show that after PSI injection the
re was a significant inhibition of NF kappa B activity in vivo that re
sulted in the appearance of fragmented (apoptotic) DNA in the CNS of r
ats. These results suggest that alteration of NF kappa B may cause apo
ptotic cell death in the rat CNS during ageing.