Quantitative immunogold study of glucose transporter (GLUT-1) in five brain regions of scrapie-infected mice showing obesity and reduced glucose tolerance

Distribution of glucose transporter (GLUT-1) in the microvascular endotheli um of scrapie-infected SJL/J hyperglycemic mice showing clinical signs of s crapie, obesity and reduced glucose tolerance was studied in five brain reg ions: cerebral cortex, hippocampus, thalamus, cerebellum and olfactory bulb . Uninfected normoglycemic SJL/J mice showing normal glucose tolerance were used as a control. Ultrathin sections of brain samples embedded at low tem perature in the hydrophilic resin Lowicryl K4M were exposed to anti-GLUT-1 antiserum followed by gold-labeled secondary antibodies. Labeling density w as recorded over luminal and abluminal plasma membranes of microvascular en dothelial cells. Ultrastructural observations revealed attenuation of the m icrovascular endothelial lining in numerous vascular profiles from brain sa mples of diabetic mice. Morphometric analysis revealed significant decrease s of the labeling density for GLUT-1 in the microvasculature of the thalamu s, cerebellum and, to a lesser degree, the hippocampus of diabetic mice. No significant differences between diabetic and non-diabetic, control mice we re observed in the microvessels supplying cerebral cortex and olfactory bul b. These findings suggest that abnormal glucose metabolism, manifested by r educed glucose tolerance and hyperglycemia, leads to impaired transvascular glucose transport in some brain regions but not in others, presumably dist urbing the function of those brain regions supplied by the affected blood m icrovessels.