Intracellular calcium changes in neuronal cells induced by Alzheimer's β-amyloid protein are blocked by estradiol and cholesterol

1. The elevation of intracellular Ca2+ levels ([Ca2+](i)) in immortalized hypothalamic neurons (GT1-7 cells) after exposure to Alzheimer's beta -amyloid protein (A betaP[25-35]) was investigated using a multisite fluorometry system. 2. The marked rise in [Ca2+](i) appeared after exposure to 5-20-muM A betaP[25-35]. Analysis of the spatiotemporal patterns of [Ca2+](i) changes revealed that the magnitude and the latency of the response to A betaP in each cell were highly heterogeneous. 3. The preadministration of 17 beta -estradiol, 17 alpha -estradiol, phloretin and cholesterol, which influence the properties of membranes, such as membrane fluidity or membrane potential, significantly decreased the rise in [Ca2+](i). 4. These findings support the idea that disruption of calcium homeostasis by A betaP channels may be the molecular basis of the neurotoxicity of A betaP and of the pathogenesis of Alzheimer's disease. It is also suggested that membrane properties may play key roles in the expression of neurotoxicity.