Antioxidants prevent amyloid peptide-induced apoptosis and alteration of calcium homeostasis in cultured cortical neurons

Beta-amyloid (A beta) is a peptide of 39-42 amino acids that is the primary component of plaques in Alzheimer's disease (AD). The mechanism by which A P expresses its neurotoxic effects may involve induction of reactive oxygen species (ROS) and elevation of intracellular free calcium levels. Cultured cortical cells were utilized to study the alterations in calcium homeostas is underlying the neurotoxic effect of A beta. Serum supplement B27 and vit amin E were effective in preventing neuronal death as assessed by lactate d ehydrogenase (LDH) release, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra zolium bromide (MTT) assay, and number of apoptotic nuclei. In addition, AP -induced cytosolic free calcium ([Ca2+](i)) was blocked by antioxidants vit amin E and U83836E, but not by N-methyl-D-aspartic acid (NMDA) receptor ant agonist MK-801, or by voltage-gated calcium channel blocker nimodipine. Tak en together, the results suggest that NMDA receptor and voltage-gated calci um channels are not involved in A beta-induced [Ca2+](i) increase. This inc rease appeared to be the result of extracellular calcium influx by some unk nown mechanisms. In addition, antioxidants such as B27 were effective in pr otecting cultured cortical neurons against A beta, and correlated with A be ta attenuation of early calcium response.