Pattern of glucose transporter (Glut 1) expression in embryonic brains is related to maturation of bood‐brain barrier tightness

Abstract

A constant supply of bloodborne glucose is vital to cerebral metabolism. Although transport of glucose into the nervous tissue, effectively separated from the blood by a functional barrier (the blood-brain barrier, BBB), is one of the essential properties of the cerebral endothelium, little is known about its metabolic regulation and developmental expression in the BBB. In this study we provide evidence by immunocytochemistry that the pattern of the brain endothelial glucose transporter in rat brains (BBB-GT), immunologically homologous with the human hepatoma (G2), human erythrocyte transporter (Glut l), changes with BBB maturation. While the neuroepithelium at embryonic days 12 and 13 shows a high incidence of immuno-detectable BBB-GT, vascularisation of the cerebral anlage and subsequent development of vascular tightness, as evidenced by intravascularly applied horseradish peroxidase and fluorescinated dextrans, is accompanied by a significant reduction of BBB-GT expression in neuroepithelial cells and confinement of BBB-GT expression to the cerebral endothelium. Immunoblots and Northern blots of embryonic brain homogenates corroborate this change in BBB-GT expression in the brain anlage at the time of BBB maturation. However, low molecular weight glucose transporters, presumed to be of non-endothelial origin, are less dramatically reduced. The development of BBB tightness, therefore, seems to play a pivotal role in the pattern of BBB-GT expression during brain differentiation.

Trans-activators Regulating Neuronal Glucose Transporter Isoform-3 Gene Expression in Mammalian Neurons

“…Based on the results of the present study, we speculate that Sp1/Sp3 may play a role in the developmental regulation of neuronal GLUT 3 expression. Thus, Sp1/Sp3 concentrations and GLUT 3 DNA bindability may change during different stages of neuronal maturation (proliferation, early embryonic versus differentiation, postnatal stage (11,12,55)). Sp1/Sp3 phosphorylation state or transcription could also be induced by certain neuron-specific stimuli (growth factors such as brain-derived neurotrophic factor and transforming growth factor-␤) similar to the induction by insulin observed in other cell systems (56,57).…”

Mouse multidrug resistance 1a/3 gene is the earliest known endothelial cell differentiation marker during blood‐brain barrier development

“…This indicates that although the complete functional barrier establishment may not occur until later, morphological changes of endothelial cells in the nervous system may occur as early as E10.5. There are several markers distinguishing endothelial cells at the BBB from other endothelial cells (Dermietzel et al, 1992;Risau, 1991;Risau et al, 1986a;Seulberger et al, 1990). However, none of these markers have been reported to be expressed in endothelial cells of E10.5 brain.…”

“…The neural environment is known to induce differentiation of BBB endothelial cells (De and Cancilla, 1980;Janzer and Raff, 1987;Stewart and Wiley, 1981) This inductive event has been characterized mainly by morphological and functional criteria such as tight junction formation and permeability changes. Several endothelial cell markers whose expression coincides with the functional establishment of BBB have been reported (Dermietzel et al, 1992;Risau et al, 1986aRisau et al, , 1986b. Some aspects of the morphological changes and marker expression can be induced by astrocyte-derived putative 0 1995 WILEY-LISS, INC. factors (De, 1981;Janzer and Raff, 1987;De and Cancilla, 1980).…”

Glucose Transporter Distribution in the Vessels of the Central Nervous System of the Axolotl Ambystoma mexicanum (Urodela: Ambystomatidae)

“…Studies on developing mammals have indicated that the neuroectodermal microenvironment commits endothelial cells to express barrier properties (Dermietzel et al, 1992;Bauer et al, 1995;Bolz et al, 1996). Concerning GLUT-1 expression in the three-dimensional microvascular pattern exemplified by mammals, this commitment appears to involve all the microvascular elements.…”

“…Its subcellular distribution was also quantified (Gerhart et al, 1989;Farrell and Pardridge, 1991). Moreover, the expression of this transporter is developmentally regulated (Dermietzel et al, 1992;Dwyer and Pardridge, 1993;Bauer et al, 1995) and developmental changes in its subcellular distribution have been quantified in embryonic and postnatal brain (Cornford et al, 1993(Cornford et al, , 1994Bolz et al, 1996).…”