title: Age and 17β-estradiol effects on blood-brain barrier tight junction and estrogen receptor proteins in ovariectomized rats.
abstract: 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-344 rats with chronic 17β-estradiol or placebo treatment. Middle-aged rats showed decreased protein expression of occludin with 17β-estradiol (55 kDa band) or placebo (45, 55, 60 kDa bands) treatment compared to respective young. In young animals, 17β-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 ERα (66 kDa) increased with 17β-estradiol treatment, while junctional adhesion molecule-A showed no change across all groups. However, ERα 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 17β-estradiol treatment alters the expression of ERα and distinct BBB TJ protein isoforms without altering functional paracellular permeability.
authors.affiliation: Pharmaceutical Sciences, School of Pharmacy, Southern Illinois University, Edwardsville, 200 University Park Drive, Edwardsville, IL 62026, USA.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Sandoval
authors.forename: Ken A
authors.initials: KA
authors.lastname: Witt
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D062507:Claudin-5; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D008565:Membrane Proteins / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D062793:Occludin; D010052:Ovariectomy; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D062507:Claudin-5; C491510:Cldn5 protein, rat; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C520495:F11r protein, rat; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D011960:Receptors, Estrogen; D004958:Estradiol; D013395:Sucrose