β-Amyloid Activates Nitric Oxide Synthesis and Causes Neuronal Death in Hippocampal Astrocytes

摘要

Abstract—Digital fluorescence imaging was used to study the effects of the amyloid-beta peptide βA (full-length peptide, βA 1-42) and its neurotoxic fragment (βA 25-35) on nitric oxide (NO) synthesis and cell via-bility in mixed cultures of rat hippocampal neurons and astrocytes. It was found that both βA 1-42 and βA25-35 stimulated NO synthesis in astrocytes, but not in neurons. L-NAME, an inhibitor of the inducible NOsynthase, blocked the effect of βA on NO production almost completely, reduced βA-induced mitochondrialdepolarization in astrocytes, and partly prevented neuronal death. The rate of NO synthesis was decreased inCa~(2+)-free medium, increased in the presence of antioxidants and the NADPH oxidase inhibitor, and decreasedin the presence of the SH-reagent thimerosal.