Glucose Transporter Isoform Expression in Huntington's Disease Brain

Abstract

Several reports have suggested a characteristic decrease in glucose use in the striatum of patients with Huntington's disease (HD) may contribute 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 cells and to a lesser extent in the brain parenchyma, whereas GLUT3 is localized primarily in neurons. Membranes prepared from postmortem samples of HD caudate and cortex and non‐HD caudate and cortex were separated on 10% sodium dodecyl sulfate‐polyacrylamide gels and probed with antisera to GLUT1 and GLUT3 by western blotting. Compared with controls, GLUT1 and GLUT3 transporter expression in caudate was decreased by three‐ and fourfold, respectively, in grade 3 of the disease. At earlier stages (grade 1), there was no significant difference in the expression of the two transporter isoforms compared with nondiseased controls. It is surprising that despite a substantial increase in glial fibrillary acidic protein immunoreactivity (an indicator of the extent of gliosis), 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 down‐regulated, perhaps reflecting the decreased metabolic demand of this brain region in HD.

Deficits in Experience-Dependent Cortical Plasticity and Sensory-Discrimination Learning in Presymptomatic Huntington's Disease Mice

“…To the best of our knowledge, there is no evidence suggesting an impairment of primary glucose metabolism in R6/1 HD mice. Additionally, in human HD patients with mild neuropathological features of HD (grade 1), there is no difference in the expression of the GLUT1 and GLUT3 glucose transporters compared with control subjects (Gamberino and Brennan, 1994). Moreover, our analysis of cortical plasticity, based on a within-subject approach rather than a comparison between WT and HD mice, dissociates defects in cortical plasticity from the separate issue of basal glucose metabolism.…”

Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease

“…Our studies suggest that HD progression could be affected by GLUT3 expression level, and functionality as in neurones glucose uptake is mainly dependent on this transporter. Indeed, a post-mortem brain study found a significant reduction in GLUT3 levels in the caudate of Grades 1 and 3 HD brain, but not in the cortex (35). …”

Enhanced Neuronal Glucose Transporter Expression Reveals Metabolic Choice in a HD Drosophila Model

“…Studies on post-mortem brain tissue or positron emission tomography imaging analyses revealed reduced cerebral metabolic activity in cortex and striatum of symptomatic HD patients and also in pre-symptomatic subjects, so even before the onset of pathological symptoms [23, 24, 25, 26]. Moreover, Gamberino and Brennan [27] described decreases in glucose transporter levels by post-mortem analysis in caudate and not in cerebral cortex of HD brains; these decreases were not closely related to brain atrophy but can be associated to changes in transporter expressions. Interestingly, in a recent study on HD patients, a correlation was found between the onset of the disease and the copy number of the GluT3 gene [28].…”