Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

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.

G-Protein-Coupled Receptor 30 Mediates Rapid Neuroprotective Effects of Estrogen via Depression of NR2B-Containing NMDA Receptors

“…1 B). Consistent with previous findings (Bae et al, 2000;Dominguez et al, 2009), the nonspecific ER agonist, E2 (1, or 10 nM), attenuated the neuronal death based on the dose induced by NMDA (F (10, 77) ϭ 10.73, p Ͻ 0.05, Tukey's test; p ϭ 0.025, 1 nM E2 vs NMDA; p Ͻ 0.01, 10 nM E2 vs NMDA; Fig. 1 B).…”

Estrogen receptor β protects against acoustic trauma in mice

“…Increased ERβ expression is known to protect the central nervous system from a wide range of disorders, including amyloid toxicity (33), cerebral ischemia (34), and glutamate toxicity (35)(36)(37)(38). The present study demonstrated that ERβ-expressing mice (WT and ERKO) are more protected against acoustic trauma compared with ERβ knockouts and ARKO mice.…”

Glutathione restores collagen degradation in TGF-β-treated fibroblasts by blocking plasminogen activator inhibitor-1 expression and activating plasminogen

“…These data further support the role of the plasminogen system in collagen degradation. Plasma-circulating plasminogen is presumed to be liver derived; however, reports also demonstrate regulatable plasminogen gene expression in extrahepatic cells/tissues (5,69,74). Interestingly, we found in this study that NIH-3T3 fibroblasts also express plasminogen (Fig.…”