ABSTRACT. The retina is protected from somatic circulation by the blood-retinal barrrier (BRB) composed of tight junctions between retinal vascular endothelial cells (the inner BRB) and those between retinal pigment epithelial cells (the outer BRB). Our recent studies showed that glial cell line-derived neurotrophic factor (GDNF) secreted from astrocytes regulates the permeability of the BBB. In the present study, we immunohistochemically examined the expression of GDNF, neurturin (NTN) and their receptors, GFR= = = =1 for GDNF and GFR= = = =2 for NTN, because the capillaries of the inner BRB show specialization very similar to the blood-brain barrier (BBB). GDNF and NTN were detected in glial fibrillary acidic protein (GFAP)-positive cells, including Müller cells. GFR= = = =1 and GFR= = = =2 were localized in von Willebrand factor-positive cells. GDNF and NTN enhanced the barrier function of endothelial cells derived from porcine brain cortex. These results strongly suggest that the barrier function of the BRB is regulated by GDNF and NTN secreted from glial cells, like the BBB.
It is well known that the blood-brain barrier (BBB) matures at approximately 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 (GFRalpha-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 GFRalpha-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 GFRalpha-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 GFRalpha-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.
We studied the gene expression of the insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and growth hormone (GH) receptor (GHR)/GH binding protein (GHBP) in liver of rats treated neonatally with monosodium glutamate (MSG). The MSG-treated rats showed severe growth retardation and obesity compared to saline-injected controls. Serum IGF-I levels in MSG-treated rats were significantly lower than in the controls after 6 weeks of age (p < 0.01). IGF-I gene expression increased with age and was significantly lower in MSG-treated rats than in the controls (p < 0.01). IGFBP-3 gene expression was unaffected by age in both MSG-treated male rats and the controls, but was less in MSG-treated female rats than in their controls between 6 to 8 weeks of age. In our study of GHR/GHBP gene expression, MSG-treated rats of both sexes displayed a distinct 1.5 kbase band encoding GHBP RNA. We speculated that these changes reflect disruption of GH secretion in in vivo experimental models. Thus, MSG-treated rats are useful as in vivo models for study of the effect of GH disruption on developmental gene expression.
The internal structures of rat fetuses on day 18.0 of pregnancy were studied by magnetic resonance imaging in 1‐mm sagittal slices. Each organ was represented as white to gray images different in tone according to the 1H proton content and the relaxation time. In solid organs, portions with high cell density were seen as white areas and those with low cell density as gray areas. In the tubular organs, the margins were imaged as white and the lumina as gray.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.