The Effects of Estradiol on Estrogen Receptor and Glutamate Transporter Expression in Organotypic Hippocampal Cultures Exposed to Oxygen--Glucose Deprivation

The molecular basis of estrogen-mediated neuroprotection against brain ischemia remains unclear. In the present study, we investigated changes in expression of estrogen receptors (ERs) α and β and excitatory amino acid transporters (EAAT) 1 and 2 in rat organotypic hippocampal slice cultures treated with estradiol and subsequently exposed to oxygen--glucose deprivation (OGD). Pretreatment with 17β-estradiol (10 nM) for 7 days protected the CA1 area of hippocampus against OGD (60 min), reducing cellular injury by 46% compared to the vehicle control group. Levels of ERα protein were significantly reduced by 20% after OGD in both vehicle- and estradiol-treated cultures, whereas ERβ was significantly up-regulated by 25% in the estradiol-treated cultures. In contrast, EAAT1 and EAAT2 levels were unchanged in response to estradiol treatment in this model of OGD. These findings suggest that estrogen-induced neuroprotection against ischemia might involve regulation of ERβ and, consequently, of the genes influenced by this receptor.Helena Cimarosti and Ross D. O’Shea, equal first authors.