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Review
. 2020 Feb 13;14:9.
doi: 10.3389/fncel.2020.00009. eCollection 2020.

A Reappraisal of GAT-1 Localization in Neocortex

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Free PMC article
Review

A Reappraisal of GAT-1 Localization in Neocortex

Giorgia Fattorini et al. Front Cell Neurosci. .
Free PMC article

Abstract

γ-Aminobutyric acid (GABA) transporter (GAT)-1, the major GABA transporter in the brain, plays a key role in modulating GABA signaling and is involved in the pathophysiology of several neuropsychiatric diseases, including epilepsy. The original description of GAT-1 as a neuronal transporter has guided the interpretation of the findings of all physiological, pharmacological, genetic, or clinical studies. However, evidence published in the past few years, some of which is briefly reviewed herein, does not seem to be consistent with a neurocentric view of GAT-1 function and calls for more detailed analysis of its localization. We therefore performed a thorough systematic assessment of GAT-1 localization in neocortex and subcortical white matter. In line with earlier work, we found that GAT-1 was robustly expressed in axon terminals forming symmetric synapses and in astrocytic processes, whereas its astrocytic expression was more diffuse than expected and, even more surprisingly, immature and mature oligodendrocytes and microglial cells also expressed the transporter. These data indicate that the era of "neuronal" and "glial" GABA transporters has finally come to a close and provide a wider perspective from which to view GABA-mediated physiological phenomena. In addition, given the well-known involvement of astrocytes, oligodendrocytes, and microglial cells in physiological as well as pathological conditions, the demonstration of functional GAT-1 in these cells is expected to provide greater insight into the phenomena occurring in the diseased brain as well as to prompt a reassessment of earlier findings.

Keywords: GABA transporters; GAT-1; astrocytes; microglia; oligodendrocytes.

Figures

Figure 1
Figure 1
(A) GAT-1 immunoreactivity in the subcortical white matter reveals the presence of numerous cells of small and medium size (arrows) and of different morphology. (B) Frequency and (C) cumulative frequency distribution of the diameter of GAT-1-positive cells. Bar: 20 μm (modified from Fattorini et al., 2017).
Figure 2
Figure 2
(A–D) Four low-magnification electron microscopic (EM) fields showing GAT-1 immunoreactivity in cerebral neocortex (layers II–III of rat parietal cortex). Colored profiles code for different GAT-1-positive cell types and/or profiles: blue, axon terminals, axon, and neuron; yellow, astrocyte and astrocytic processes; green, oligodendrocyte; red, microglial cell. Framed regions in (A–D) are reproduced and enlarged, in the lowest portion of the figure. Bar: 2.5 μm for (A–D); 0.8 and 1 μm for enlarged frames of (A) and (B–D), respectively (modified from Melone et al., ; Fattorini et al., 2017, 2020).

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