Enhanced expression of ERalpha in astrocytes modifies the response of cortical neurons to beta-amyloid toxicity.
Estrogen receptor alpha (ERalpha) is over-expressed in reactive glia under conditions of neuronal damage. To elucidate the functional significance of ERalpha overexpression, an in vitro model of reactive astrocytes with enhanced expression of ERalpha 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 17beta-estradiol (17betaE2) or transferring of 17betaE2-pretreated astrocytes, caused a greater neuroprotective effect compared to the respective control conditions, although reactive glia resulted being per se neuroprotective. Blockade of ERalpha overexpression by the ER antagonist ICI182,780 was not successful as ICI182,780 behaved as an agonist. However, complete prevention of 17betaE2 effect by ICI182,780 produced an increased sensitivity of neurons to beta-amyloid toxicity. A similar effect was observed when ERalpha knock-down was induced by siRNA. It is suggested that increased ERalpha expression in reactive glia may have a role in limiting neuronal damage.
Carbonaro
Viviana
V
Department of Experimental and Clinical Pharmacology, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
Caraci
Filippo
F
Giuffrida
Maria Laura
ML
Merlo
Sara
S
Canonico
Pier Luigi
PL
Drago
Filippo
F
Copani
Agata
A
Sortino
Maria Angela
MA
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D000077267:Fulvestrant; D055785:Gene Knockdown Techniques; D009474:Neurons / Q000502:physiology*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D000077267:Fulvestrant; D004958:Estradiol