Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In th e present study, we examined the neuroprotective spectrum of estrogen again st excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosi s of neurons in mouse cortical cultures. 17 beta-estradiol as well as 17 al pha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 mu/M FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 mu M N-methyl-D-aspartate (NMDA) and serum-deprivation i nduced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by A beta 25-35. However, all these neuroprotective effects were m ediated by the anti-oxidative action of estrogens. When oxidative stress wa s blocked by an antioxidant trolox, estrogens did not show any additional p rotection. Addition of a specific estrogen receptor antagonist ICI182,780 d id not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injur ies mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors medi ate neuroprotection.