J Korean Med Sci.  2000 Jun;15(3):327-336. 10.3346/jkms.2000.15.3.327.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Affiliations
  • 1National Creative Research Initiative Center for the Study of Central Nervous System Zinc and Department of Neurology, University of Ulsan, College of Medicine, Seoul, Korea.

Abstract

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Keyword

Estrogens; Neuroprotective Agents; Antioxidants; Alzheimer Disease

MeSH Terms

Amyloid beta-Protein/pharmacology
Animal
Antioxidants/pharmacology*
Antioxidants/metabolism
Apoptosis/drug effects*
Cells, Cultured
Chelating Agents/pharmacology
Chromans/pharmacology
Estradiol/pharmacology
Estrogens/pharmacology*
Estrogens/metabolism
Estrone/pharmacology
Ethylenediamines/pharmacology
Excitatory Amino Acid Agonists/pharmacology
Ferric Compounds/pharmacology
Lactate Dehydrogenase/analysis
Mice
N-Methylaspartate/pharmacology
Neurons/metabolism
Neurons/drug effects*
Neurons/cytology
Organ of Corti/cytology
Peptide Fragments/pharmacology
Staurosporine/pharmacology
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