Central nervous system DNA fragmentation induced by the inhibition of nuclear factor kappa B

Ageing of the central nervous system (CNS) is characterized by a progressive apoptotic loss of neurons that may be in part due to impaired neurotrophin signaling mediated by such elements as the transcription factor nuclear factor kappa B (NFkappaB). To support this hypothesis, we inhibited nuclear translocation of NFkappaB in vivo by injecting a proteasome inhibitor (PSI) directly in the CNS lateral ventricle of rats and then measured fragmented DNA in various CNS areas as an index of ongoing apoptosis. Our results show that after PSI injection there was a significant inhibition of NFkappaB activity in vivo that resulted in the appearance of fragmented (apoptotic) DNA in the CNS of rats. These results suggest that alteration of NFkappaB may cause apoptotic cell death in the rat CNS during ageing.