Enhanced expression of ERα in astrocytes modifies the response of cortical neurons to β-amyloid toxicity

Estrogen receptor alpha (ER alpha) is over-expressed in reactive glia under conditions of neuronal damage. To elucidate the functional significance of ER alpha overexpression, an in vitro model of reactive astrocytes with enhanced expression of ER alpha was obtained by growth in G5 culture supplement. Exposure of cortical neurons to beta-amyloid in the presence of either conditioned medium from reactive astrocytes previously treated with 17 beta-estradiol (17 beta E2) or transferring of 17 beta E2-pretreated astrocytes, caused a greater neuroprotective effect compared to the respective control conditions, although reactive glia resulted being per se neuroprotective. Blockade of ER alpha overexpression by the ER antagonist ICI182,780 was not successful 780 behaved as an agonist. However, complete prevention of 17 beta E2 effect by ICI182,780 produced an increased sensitivity of neurons to beta-amyloid toxicity. A similar effect was observed when ER alpha knockdown was induced by siRNA. It is suggested that increased ER alpha expression in reactive glia may have a role in limiting neuronal damage. (C) 2008 Elsevier Inc. All rights reserved.