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Cell Mol Neurobiol. 2001 Feb;21(1):1-13.

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

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  • 1Department of Molecular & Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu-shi, Japan. kawamasa@tmin.ac.jp

Abstract

1. The elevation of intracellular Ca2+ levels ([Ca2+]i) in immortalized hypothalamic neurons (GT1-7 cells) after exposure to Alzheimer's beta-amyloid protein (AbetaP[25-35]) was investigated using a multisite fluorometry system. 2. The marked rise in [Ca2+]i appeared after exposure to 5-20-microM AbetaP[25-35]. Analysis of the spatiotemporal patterns of [Ca2+]i changes revealed that the magnitude and the latency of the response to AbetaP in each cell were highly heterogeneous. 3. The preadministration of 17beta-estradiol, 17alpha-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 AbetaP channels may be the molecular basis of the neurotoxicity of AbetaP and of the pathogenesis of Alzheimer's disease. It is also suggested that membrane properties may play key roles in the expression of neurotoxicity.

PMID:
11440193
[PubMed - indexed for MEDLINE]
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