CENTRAL-NERVOUS-SYSTEM DNA FRAGMENTATION INDUCED BY THE INHIBITION OFNUCLEAR FACTOR-KAPPA-B

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.