ESTROGEN BLOCKS NEUROTOXIC EFFECTS OF BETA-AMYLOID(1-42) AND INDUCES NEURITE EXTENSION ON B103 CELLS

Clinical studies have shown that estrogen replacement therapy is assoc iated with reduced risk of Alzheimer's disease (AD). We tested whether or not estrogen blocks neurotoxic effects of beta-amyloid (1-42) (A b eta(1-42)) on cultured B103 cells. A beta(1-42) (1 mu M) induced typic al necrotic cell death, as revealed by light and electron microscopic examinations. Go-administration of estrogen not only blocked A beta(1- 42) toxicity to a large degree, but also enhanced neurite extension. P retreatment with estrogen was even more effective in blocking A beta(1 -42) toxicity. When added 18 h after the beginning of A beta(1-42) tre atment, estrogen was still effective in halting the progress of cell d eath and enhancing neurite extension. The protection against A beta(1- 42)-induced neuronal death by estrogen was unlikely due to a blockade of lipid peroxidation injury, since estrogen completely failed to atte nuate ferrous chloride-induced cell death. These results demonstrate t hat estrogen blocks A beta(1-42)-induced neurotoxicity and enhances ne urite extension on B103 cells, both of which may well be underlying me chanisms of beneficial effects of estrogen in AD. (C) 1997 Elsevier Sc ience Ireland Ltd.