We studied the expression of γ-aminobutyric acid plasma membrane transporters GAT-1 and GAT-3 in the cerebral cortex of rats following transient middle cerebral artery occlusion. GAT-1 immunoreactivity exhibited minor changes and immunoblotting studies showed that the protein levels were unchanged. By contrast, GAT-3 immunoreactivity, which is normally expressed exclusively by distal astrocytic processes, was remarkably altered: (1) GAT-3-positive puncta were reduced in the perilesional cortex and disorganized in the remaining regions; (2) numerous GAT-3-positive cells were observed, mostly in the perilesional cortex; they were all NeuN positive and most of them were identified as pyramidal neurons. Immunoblotting studies showed that GAT-3 levels were not significantly altered. Confocal studies showed that virtually all GAT-3-positive neurons in the perilesional cortex were TUNEL negative and coexpressed heat shock protein 70 kDa. These findings suggest that ischemia triggers a novel neuronal expression of GAT-3 that is greatest in the perilesional cortex and may contribute to the reported reduction in GABAergic inhibition.
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