Expression of GFR alpha-1, receptor for GDNF, in rat brain capillary during postnatal development of the BBB

It is well known that the blood-brain barrier (BBB) matures at similar to 2 wk after birth in the rat. Recently, we showed that glial cell line-derive d neurotrophic factor (GDNF) enhances the barrier function of porcine endot helial cells forming the BBB in culture. In the present study, we examined the relation between permeability of the BBB, using Evans blue as a tracer, and expression of the GDNF family receptor (GFR alpha-1) during postnatal development of the BBB. Morphometric analysis showed that exudation of Evan s blue from capillaries of the cerebral cortex progressively decreased unti l postnatal day 21. Inversely, immunohistochemical examinations showed expr ession of GFR alpha-1 in the capillaries at postnatal day 3 and expression that reached the same levels as observed in adult rats by postnatal day 10. However, c-ret, which is thought to mediate a signal evoked by binding of GDNF to GFR alpha-1, was not expressed in the capillaries of the brain cort ex in 3-mo-old rats. On the other hand, the tight junction proteins occludi n and ZO-1 appeared to be fully expressed at birth. The reciprocal relation between GFR alpha-1 expression and the permeability of the BBB strongly su ggests active participation of GDNF in postnatal development of the BBB, al though the mechanism(s) involved is still veiled.