Beta amyloid activates synthesis of nitric oxide in hyppocampal astrocytes and causes death of neurons

Digital fluorescence imaging was used to examine the action of amyloid beta peptides (PA, full length peptide beta A 1-42, and the neurotoxic fragment 25-35) on NO production and cell viability in mixed cultures of astrocytes and neurons from rat hippocampus. We have found that both PA 1-42 and PA 25-35 induced the production of NO in astrocytes but not in neurons. Inhibitor of iNOS, L-NAME, completely blocked the effect of PA on NO production, reduced beta A-induced mitochondrial depolarization in astrocytes, and partially prevented neuronal death. The production of NO was dependent on the presence of Ca2+ in the external medium. Antioxidants and an inhibitor of NADPH-oxidase increased the rate of NO production, while thimerosal (SH-reagent) reduced the NO production rate.