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

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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) 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.

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Acknowledgements

Supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brazil), which provided HC a scholarship for research towards Ph.D. in Australia, and by Neurosciences Victoria (NMJ) and a Program Grant (#236805) from the NH&MRC (Australia), of which PMB is a Research Fellow. We thank Dr. D. Pow (University of Queensland) for the gifts of glutamate transporters antibodies.

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Authors and Affiliations

  1. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Allegre, RS, Brazil

    Helena Cimarosti, Ana Paula Horn, Fabrício Simão, Lauren L. Zamin, Melissa Nassif, Rudimar Frozza, Carlos Alexandre Netto & Christianne Salbego

  2. Brain Injury and Repair Program, Howard Florey Institute, University of Melbourne, 3010, Melbourne, VIC, Australia

    Helena Cimarosti, Ross D. O’Shea, Nicole M. Jones & Philip M. Beart

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  1. Helena Cimarosti
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  2. Ross D. O’Shea
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  3. Nicole M. Jones
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  4. Ana Paula Horn
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  5. Fabrício Simão
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  6. Lauren L. Zamin
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  7. Melissa Nassif
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  8. Rudimar Frozza
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  9. Carlos Alexandre Netto
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  10. Philip M. Beart
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  11. Christianne Salbego
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Correspondence to Philip M. Beart.

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Helena Cimarosti and Ross D. O’Shea, equal first authors.

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Cimarosti, H., O’Shea, R.D., Jones, N.M. et al. The Effects of Estradiol on Estrogen Receptor and Glutamate Transporter Expression in Organotypic Hippocampal Cultures Exposed to Oxygen--Glucose Deprivation. Neurochem Res 31, 483–490 (2006). https://doi.org/10.1007/s11064-006-9043-9

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