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

Abstract

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) alpha and beta 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 17beta-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 ERalpha protein were significantly reduced by 20% after OGD in both vehicle- and estradiol-treated cultures, whereas ERbeta 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 ERbeta and, consequently, of the genes influenced by this receptor.

Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: A human model to study neurological diseases

“…One of these advantages is that human tumor and nontumor brain tissue can be maintained for a prolonged period of time. This amount of time is necessary for conducting long-term experiments such as pharmacological interventions (Eyupoglu et al 2006;Oest et al 2006;Sundstrom et al 2005), cytoarchitecture evaluation (Michelini et al 2005), migration assays (Jung et al 2002;Valster et al 2005), and disease model evaluation (Cimarosti et al 2006;Duveau et al 2005;Shahani et al 2006;Stein et al 2004). Another benefit is that this model utilizes otherwise discarded tissue to create an experimental model that closely represents what actually occurs in humans, in vivo.…”

“…Normal human explants, as with rodents, can be used to study cell migration (Jung et al 2002;Valster et al 2005), drug toxicity (Eyupoglu et al 2006;Oest et al 2006), and various disease models including epilepsy (Duveau et al 2005;Hanson et al 2006), stroke (Cavaliere et al 2006;Cimarosti et al 2006;Shirakawa et al 2006), and Alzheimer's disease (Shahani et al 2006;Stein et al 2004). In addition, tumor explants can be used to study cytoarchitecture, tumor and non-tumor cell migration, and the efficacy of various pharmacologic interventions.…”

Neuroprotective Effects of Genistein in Mongolian Gerbils: Estrogen Receptor–β Involvement

“…This finding confirms the mildselective agonist property of genistein for ERβ with more than 7-fold higher binding affinity for ERβ than ERα (22), thus avoiding unwanted severe ERα agonist side effects such as cancer promotion. An ER-mediated neuroprotection in a model of global cerebral ischemia has been shown in female rats pre-treated with the ERβ agonist diarylpropionitrile but not with the ERα agonist propylpyrazole triol (61) and in vitro in a model of oxygen glucose deprivation (62).…”

Neuroprotection and Estrogen Receptors

“…In contrast, a recent study that employed both ER subtype-selective agonists and BERKO mice concluded that ERβ mediates 17βE 2 -induced protection against NMDA-induced toxicity in hippocampal slices [115]. Interestingly, 17βE 2 increased protein levels of both ERα and ERβ in the latter study, whereas Cimarosti et al [116] reported selective upregulation of ERβ in 17βE 2 -treated hippocampal explants subjected to oxygen-glucose deprivation.…”