β-amyloid-induced cytotoxicity, peroxide generation and blockade of glutamate uptake in cultured astrocytes

β-Amyloid (βA) is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated βA-induced cytotoxicity, peroxide generation and glutamate (Glu) uptake in cultured astrocytes. Twenty-four hours after a single addition of either βA 25-35 or βA 1-40 there was a concentration-dependent decrease in viability. Catalase or vitamin E showed no protective effect against βA 25-35 Dithiothreitol (DTT), N-acetylcysteine (NAC) and cyclosporine A significantly prevented the toxic effects of both βA 25-35 and peroxide, while inhibition of peroxide detoxifying enzymes enhanced toxicity. Exposure to βA 25-35 or βA 1-40 increased peroxides at 2 h and 24 h, which was prevented by DTT and NAC, but not vitamin E. βA 25-35 inhibited Glu uptake in astrocytes and neurons in culture. Following exposure of neurons to βA for 24 h there was decreased uptake and increased Glu levels in the culture medium, that resulted in gradual excitotoxicity.