Age and 17β-estradiol effects on blood-brain barrier tight junction and estrogen receptor proteins in ovariectomized rats

Age and estrogen levels alter blood-brain barrier (BBB) tight junction (TJ) regulation, impacting brain homeostasis and pathological outcomes. This examination evaluated BBB TJ and estrogen receptor (ER) protein expression changes in young (8-10 week) and middle-aged (10-12 month) ovariectomized female Fisher-394 rats with chronic 17 beta-estradiol or placebo treatment. Middle-aged rats showed decreased protein expression of occludin with 17 beta-estradiol (55 kDa band) or placebo (45, 55, 60 kDa bands) treatment compared to respective young. In young animals, 17 beta-estradiol treatment increased expression of the occludin 55 kDa band over placebo; however, this effect was lost in the middle-aged animals. In both young and middle-aged animals, expression of claudin-5 (23,32 kDa bands) and ER alpha (66 kDa) increased with 17 beta-estradiol treatment, while junctional adhesion molecule-A showed no change across all groups. However, ER alpha expression (66 kDa) was significantly reduced in the middle-aged animals compared to young placebo treated animals. Measurement of BBB TJ permeability via in situ perfusion of 14 C-sucrose showed no change with age or treatment. Our results show that increasing age and 17 beta-estradiol treatment alters the expression of ER alpha and distinct BBB TJ protein isoforms without altering functional paracellular permeability. (C) 2010 Elsevier Inc. All rights reserved.