As neurons rely almost exclusively on glucose as an energy substrate, glucose transport is of critical importance to cerebral function. Two specific facultative glucose transporters, GT1 and -3, predominate in brain, with the latter exclusively expressed by neurons, whereas GT1 is expressed by astrocytes and vascular elements. Little is known about the regulation of these transporters at the genetic level or the extent to which their expression may change in response to acute or chronic changes in metabolic demands. Thus, we employed in situ hybridization to evaluate changes in glucose transporter gene expression in the rat brain in response to ischemia induced by middle cerebral artery occlusion (MCAO). The most remarkable responses were demonstrated by GT1, which within an hour of ischemic insult demonstrated a global increase in gene expression throughout the forebrain. In the ensuing hours, GT1 expression further intensified and became lateralized to the lesioned hemisphere, with normalization of expression contralaterally. Increased GT1 mRNA levels were found in astroglia and micro vessels and were also present in distinct neuronal populations, including the piriform cortex, dentate gyrus, and medial habenula, which normally do not express GT1 mRNA. By 24 h post-MCAO, glial cells of the ipsilateral cortex surrounding the infarct zone still demonstrated elevated GT1 mRNA levels, but expression had returned to baseline in neurons. Interestingly, it was not until GT1 expression had subsided (24 h post-MCAO), that there was a modest increase in neuronal GT3 gene expression in the affected hemisphere. GT2 and GT4 mRNAs were not detected in the rat brain under normal conditions or after ischemia. These data demonstrate that ischemia induces an immediate and sustained increase in brain GT1 gene expression in both glial cells and neurons. This augmentation of GT1 expression could represent a defensive strategy aimed at repletion of the brain's energy stores and stabilization of neuronal membrane potential.
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