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Estrogen receptor-mediated resveratrol actions on blood-brain barrier of ovariectomized mice

Title
Estrogen receptor-mediated resveratrol actions on blood-brain barrier of ovariectomized mice
Authors
Shin, Jin A.Oh, SeikwanAhn, Jung-HyuckPark, Eun-Mi
Ewha Authors
오세관박은미안정혁
SCOPUS Author ID
오세관scopus; 박은미scopus; 안정혁scopus
Issue Date
2015
Journal Title
NEUROBIOLOGY OF AGING
ISSN
0197-4580JCR Link1558-1497JCR Link
Citation
vol. 36, no. 2, pp. 993 - 1006
Keywords
Blood-brain barrier permeabilityEstrogen receptorsIschemic strokeOvariectomyResveratrolTight junction protein
Publisher
ELSEVIER SCIENCE INC
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
To test whether resveratrol provides benefits via estrogen receptors (ERs) in the blood-brain barrier of estrogen-deficient females, ovariectomized mice were treated with resveratrol then were subjected to transient middle cerebral artery occlusion (MCAO). Compared with vehicle treatment, resveratrol reduced infarct volume and neurologic deficits after MCAO. Basal tight junction (TJ) protein levels in the brain were increased by resveratrol. After MCAO, blood-brain barrier breakdown reduced levels of TJ proteins, and induction of HIF-1 alpha and VEGF were attenuated by resveratrol. These effects were reversed by the ERs antagonist, ICI182,780. In mouse brain, endothelial cells (bEnd.3) exposed to hypoxia, resveratrol treatment protected the cells against cytotoxicity, increases of paracellular permeability and changes in levels of TJ protein and HIF-1 alpha/VEGF proteins. These effects were reversed by ICI182,780 but not by specific ER alpha or ER beta antagonists, indicating nonspecific ER mediated effects. Altogether, these results showed that neuroprotective effects of resveratrol in ovariectomized mice were mediated by ERs and associated with tightening of blood-brain barrier, suggesting that resveratrol can be an alternative to estrogens to protect the brains of estrogen-deficient females against ischemic insult. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.neurobiolaging.2014.09.024
Appears in Collections:
의과대학 > 의학과 > Journal papers
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