Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid β-Peptide Toxicity in Hippocampal Neurons
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 66, Issue 5, pages 1836–1844, May 1996
How to Cite
Goodman, Y., Bruce, A. J., Cheng, B. and Mattson, M. P. (1996), Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid β-Peptide Toxicity in Hippocampal Neurons. Journal of Neurochemistry, 66: 1836–1844. doi: 10.1046/j.1471-4159.1996.66051836.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Resubmitted manuscript received November 27, 1995; accepted December 4, 1995.
- Alzheimer's disease;
- Confocal laser scanning microscope;
- Free radicals;
- Lipid peroxidation;
- Neuronal death;
- Thiobarbituric acid
Abstract: Steroid hormones, particularly estrogens and glucocorticoids, may play roles in the pathogenesis of neurodegenerative disorders, but their mechanisms of action are not known. We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid β-peptide (Aβ) toxicity. The toxicity of each insult was significantly attenuated in cultures pretreated for 2 h with 100 nM-10 µM 17β-estradiol, estriol, or progesterone. In contrast, corticosterone exacerbated neuronal injury induced by glutamate, FeSO4, and Aβ. Several other steroids, including testosterone, aldosterone, and vitamin D, had no effect on neuronal vulnerability to the different insults. The protective actions of estrogens and progesterone were not blocked by actinomycin D or cycloheximide. Lipid peroxidation induced by FeSO4 and Aβ was significantly attenuated in neurons and isolated membranes pretreated with estrogens and progesterone, suggesting that these steroids possess antioxidant activities. Estrogens and progesterone also attenuated Aβ- and glutamate-induced elevation of intracellular free Ca2+ concentrations. We conclude that estrogens, progesterone, and corticosterone can directly affect neuronal vulnerability to excitotoxic, metabolic, and oxidative insults, suggesting roles for these steroids in several different neurodegenerative disorders.