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) 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.
Cimarosti
Helena
H
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Allegre, Brazil .
O'Shea
Ross D
RD
Jones
Nicole M
NM
Horn
Ana Paula
AP
Simão
Fabrício
F
Zamin
Lauren L
LL
Nassif
Melissa
M
Frozza
Rudimar
R
Netto
Carlos Alexandre
CA
Beart
Philip M
PM
Salbego
Christianne
C
D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D000860:Hypoxia; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D004958:Estradiol; D005947:Glucose