THE HUMAN BLOOD-BRAIN-BARRIER GLUCOSE-TRANSPORTER (GLUT1) IS A GLUCOSE-TRANSPORTER OF GRAY-MATTER ASTROCYTES

Human and monkey brain sections were examined by immunohistochemical l ight and electron microscopy to determine the distribution of GLUT1, a glucose transporter isoform associated with erythrocytes and endothel ial cells of the human blood-brain barrier. Protein immunoblotting of fractionated human brain membranes was performed to determine the dist ribution of molecular forms of the transporter. GLUT1 staining was abu ndant in erythrocytes and cerebral endothelium of gray and white matte r but was also present diffusely in gray matter neuropil when viewed b y light microscopy. Immunoelectron microscopy confirmed the gray matte r and vascular localization of GLUT1, with specific GLUT1 staining see n in erythrocytes, gray and white matter endothelial cells, astrocyte foot processes surrounding gray matter blood vessels, and in astrocyte processes adjacent to synaptic contacts. No astrocytic staining was i dentified in white matter. Astrocyte GLUT1 staining was identified onl y in mature gray matter regions; undifferentiated regions of preterm ( 22-23 weeks gestation) cortex had GLUT1 staining only in blood vessels and erythrocytes, as did germinal matrix. Immunoblots of adult human frontal cortex revealed that two forms of GLUT1 (45 and 52 kDa) were p resent in unfractionated brain homogenates. Immunoblots of vessel-depl eted frontal lobe revealed only the 45 kDa form in gray matter fractio ns, and depleted in membranes prepared from white matter regions. We c onclude that the GLUT1 isoform of glucose transporter is present both in endothelium of the blood-brain barrier and in astrocytes surroundin g gray matter blood vessels and synapses. Furthermore, the form presen t in astrocytes is likely to have a lower molecular weight than the fo rm found in cerebral endothelium. The GLUT1 transporter may play an im portant role not only in astrocyte metabolism, but also in astrocyte-a ssociated pathways supporting neuronal energy metabolism. (C) 1995 Wil ey-Liss, Inc.