Aging increases amyloid β-peptide-induced 8-iso-prostaglandin F2α release from rat brain

In order to investigate whether amyloid β-peptide-induced oxidative damage in the brain could be related to aging, we studied the release of 8-iso-prostaglandin (PG)F2α, a stable marker of cellular oxidative stress, in brain synaptosomes from Wistar rats of different ages (3, 6, 12, 18 months old), both basally and after amyloid β-peptide (1–40) perfusion. We found that basal release of 8-iso-PGF2α was not significantly different among all age groups of rats. Either phospholipase A2 activation induced by calcium ionophore A23187 (10 nM) or amyloid β-peptide (5 μM) did not modify isoprostane release, when these substances were used alone. In contrast, amyloid β-peptide (1–5 μM) preincubation caused a dose-dependent increase of A23187-stimulated 8-iso-PGF2α release in each age group, which was also strikingly correlated to aging of rats. Furthermore, ferric ammonium sulfate stimulates isoprostane production to levels comparable to those induced by amyloid β-peptide. In conclusion, although 8-iso-PGF2α production from rat brain synaptosomes is independent from aging in the basal state, aging renders neurons more vulnerable to amyloid β-peptide-induced oxidative toxicity.