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

Estrogen receptor α (ERα) is over-expressed in reactive glia under conditions of neuronal damage. To elucidate the functional significance of ERα overexpression, an in vitro model of reactive astrocytes with enhanced expression of ERα was obtained by growth in G5 culture supplement. Exposure of cortical neurons to β-amyloid in the presence of either conditioned medium from reactive astrocytes previously treated with 17β-estradiol (17βE2) or transferring of 17βE2-pretreated astrocytes, caused a greater neuroprotective effect compared to the respective control conditions, although reactive glia resulted being per se neuroprotective. Blockade of ERα overexpression by the ER antagonist ICI182,780 was not successful as ICI182,780 behaved as an agonist. However, complete prevention of 17βE2 effect by ICI182,780 produced an increased sensitivity of neurons to β-amyloid toxicity. A similar effect was observed when ERα knock-down was induced by siRNA. It is suggested that increased ERα expression in reactive glia may have a role in limiting neuronal damage.