GAT‐1 mediated GABA uptake in rat oligodendrocytes. Issue 3 (10th January 2017) - Fattorini, Giorgia
Abstract : Stimulated by the results of a recent paper on the effects of tiagabine, a selective inhibitor of the main GABA transporter GAT‐1, on oligodendrogenesis, we verified the possibility that GAT‐1 may be expressed in oligodendrocytes using immunocytochemical methods and functional assays. Light microscopic analysis of the subcortical white matter of all animals revealed the presence of numerous GAT‐1+ cells of different size (from 3 to 29 µm) and morphology. An electron microscope analysis revealed that, besides fibrous astrocytes and interstitial neurons, GAT‐1 immunoreactivity was present in immature and mature oligodendrocytes. Co‐localization studies between GAT‐1 and markers specific for oligodendrocytes (NG2 and RIP) showed that about 12% of GAT‐1 positive cells in the white matter were immature oligodendrocytes, while about 15% were mature oligodendrocytes. In vitro functional assays showed that oligodendrocytes exhibit tiagabine‐sensitive Na + ‐dependent GABA uptake. Although relationships between GABA and oligodendrocytes have been known for many years, this is the first demonstration that GAT‐1 is expressed in oligodendrocytes. The present results on the one hand definitely closes the era of "neuronal" and "glial" GABA transporters, on the other they suggest that oligodendrocytes may contribute to pathophysiology of the several diseases in which GAT‐1 have been implicated to date. GLIA 2017;65:514–522 Main Points: About 26% of GAT‐1+ cells in subcortical white matter are mature and immature oligodendrocytes. Functional studies showed that oligodendrocytes exhibit Na+ ‐dependent GABA uptake, and that it was significantly inhibited by tiagabine.