Effect of estrogen on the expression of occludin in ovariectomized mouse brain

Abstract

The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), formed by interactions of tight junctions (TJs) in the endothelia or the choroids plexus, respectively, are important diffusion barriers between systemic circulation and neural tissue of the central nervous system (CNS). Epidemiological incidence of degenerative changes in the CNS is significantly higher in postmenopausal women than in men, suggesting an important role of ovarian steroids for CNS integrity in women. To elucidate the role estrogen in the maintenance of paracellular diffusion barriers in the CNS, changes in the expression of occludin, a TJ protein, following ovariectomy (OVX), as well as the effect of estrogen on the expression of occludin in OVX female brain, were examined in mice. Immunoreactivity of occludin was found in brain endothelial capillaries, choroids plexus, ependyma, and aqueduct. In OVX brain, expression of occludin mRNA and protein was decreased a little but significantly relative to a sham control brain at the estrous stage. Estrogen (170 estradiol) significantly up-regulated occludin mRNA levels in OVX mice. Together, these results suggest that occludin is an important structural element in both the BBB and BCSFB, and that expression of occludin in female brain tissue is sensitive to estrogen levels.