Ontogeny of tight junction protein expression in the ovine cerebral cortex during development

Tight junctions of the blood-brain barrier are composed of transmembrane and associated cytoplasmic proteins. The transmembrane claudin proteins form the primary seal between endothelial cells and junctional adhesion molecules (JAMs) regulate tight junction formation. We have previously shown that claudin-1, claudin-5, zonula occludens (ZO)-1, and ZO-2 exhibit differential developmental regulation from 60% of gestation up to maturity in adult sheep. The purpose of the current study was to examine developmental changes in claudin-3, -12, and JAM-A protein expression in cerebral cortices of fetuses at 60%, 80%, and 90% gestation, and in newborn and adult sheep. We also examined correlations between changes in endogenous cortisol levels and tight junction protein expression in cerebral cortices of the fetuses. Claudin-3, -12 and JAM-A expressions were determined by Western immunoblot. Claudin-3 and -12 were lower (P<0.01) at 60%, 80%, 90% and in newborns than in adults, and JAM-A was lower in adults than in fetuses at 80% and 90% gestation. Claudin-3 expression demonstrated a direct correlation with increasing plasma cortisol levels (r=0.60, n=15, P<0.02) in the fetuses. We conclude that: claudin-3, -12 and JAM-A are expressed as early as 60% of gestation in ovine cerebral cortices, exhibit differential developmental regulation, and that increasing endogenous glucocorticoids modulate claudin-3 expression in the fetus.