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

Utsumi, Hiroyuki, Hideki Chiba, Yasuhiro Kamimura, Makoto Osanai, Yo Igarashi, Hirotoshi Tobioka, Michio Mori, and Norimasa Sawada. Expression of GFRa-1, receptor for GDNF, in rat brain capillary during postnatal development of the BBB. Am J Physiol Cell Physiol 279: C361–C368, 2000.—It is well known that the bloodbrain barrier (BBB) matures at ;2 wk after birth in the rat. Recently, we showed that glial cell line-derived neurotrophic factor (GDNF) enhances the barrier function of porcine endothelial 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 (GFRa-1) during postnatal development of the BBB. Morphometric analysis showed that exudation of Evans blue from capillaries of the cerebral cortex progressively decreased until postnatal day 21. Inversely, immunohistochemical examinations showed expression of GFRa-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 GFRa-1, was not expressed in the capillaries of the brain cortex in 3-mo-old rats. On the other hand, the tight junction proteins occludin and ZO-1 appeared to be fully expressed at birth. The reciprocal relation between GFRa-1 expression and the permeability of the BBB strongly suggests active participation of GDNF in postnatal development of the BBB, although the mechanism(s) involved is still veiled.