Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult and aged rat hippocampus

It is suggested that the fibrillar amyloid beta peptide (A beta) in brain p lays a direct role in neurodegeneration in Alzheimer's disease, probably th rough activation of reactive oxygen species formation. Free radicals and nu merous neurotoxins elicit DNA damage that subsequently activates poly(ADP-r ibose) polymerase (PARP, EC 2.4.2.30). In this study the effect of neurotox ic fragment (25-35) of full length A beta peptide on PARP activity in adult and aged rat hippocampus was investigated. In adult (4 month old) rat hipp ocampus the A beta 25-35 peptide significantly enhanced PARP activity by ab out 80% but had no effect on PARP activity in cerebral cortex and in hippoc ampus from aged (24-27 month old) rats. The effect of A beta peptide was re duced by half by the nitric oxide synthase inhibitor N-nitro-L-arginine. St imulation of glutamate receptor(s) itself enhanced PARP activity by about 8 0% in adult hippocampus. However, A beta 25-35 did not exert any additional stimulatory effect. These results indicate that A beta, through NO and pro bably other free radicals, induces activation of DNA bound PARP activity ex clusively in adult but not in aged hippocampus.