GLUCOSE-TRANSPORTER ISOFORM EXPRESSION IN HUNTINGTONS-DISEASE BRAIN

Several reports have suggested a characteristic decrease in glucose us e in the striatum of patients with Huntington's disease (HD) may contr ibute to the cellular atrophy of the caudate and putamen. We examined the expression of the two major glucose transporter isoforms of brain, GLUT1 and GLUT3. GLUT1 is found largely in capillary endothelial cell s and to a lesser extent in the brain parenchyma, whereas GLUT3 is loc alized primarily in neurons. Membranes prepared from postmortem sample s of HD caudate and cortex and non-HD caudate and cortex were separate d on 10% sodium dodecyl sulfate-polyacrylamide gels and probed with an tisera to GLUT1 and GLUT3 by western blotting. Compared with controls, GLUT1 and GLUT3 transporter expression in caudate was decreased by th ree- and fourfold, respectively, in grade 3 of the disease. At earlier stages (grade 1), there was no significant difference in the expressi on of the two transporter isoforms compared with nondiseased controls. It is surprising that despite a substantial increase in glial fibrill ary acidic protein immunoreactivity (an indicator of the extent of gli osis), glucose transporter expression was diminished significantly in HD caudate. The results suggest in the absence of a significant number of neurons, as in grade 3, glial cell GLUT1 and GLUT3 expression is d own-regulated, perhaps reflecting the decreased metabolic demand of th is brain region in HD.