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A Reappraisal of GAT-1 Localization in Neocortex

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 guid...

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Autores principales: Fattorini, Giorgia, Melone, Marcello, Conti, Fiorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031676/
https://www.ncbi.nlm.nih.gov/pubmed/32116556
http://dx.doi.org/10.3389/fncel.2020.00009
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author Fattorini, Giorgia
Melone, Marcello
Conti, Fiorenzo
author_facet Fattorini, Giorgia
Melone, Marcello
Conti, Fiorenzo
author_sort Fattorini, Giorgia
collection PubMed
description 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.
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spelling pubmed-70316762020-02-28 A Reappraisal of GAT-1 Localization in Neocortex Fattorini, Giorgia Melone, Marcello Conti, Fiorenzo Front Cell Neurosci Cellular Neuroscience 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. Frontiers Media S.A. 2020-02-13 /pmc/articles/PMC7031676/ /pubmed/32116556 http://dx.doi.org/10.3389/fncel.2020.00009 Text en Copyright © 2020 Fattorini, Melone and Conti. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Fattorini, Giorgia
Melone, Marcello
Conti, Fiorenzo
A Reappraisal of GAT-1 Localization in Neocortex
title A Reappraisal of GAT-1 Localization in Neocortex
title_full A Reappraisal of GAT-1 Localization in Neocortex
title_fullStr A Reappraisal of GAT-1 Localization in Neocortex
title_full_unstemmed A Reappraisal of GAT-1 Localization in Neocortex
title_short A Reappraisal of GAT-1 Localization in Neocortex
title_sort reappraisal of gat-1 localization in neocortex
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031676/
https://www.ncbi.nlm.nih.gov/pubmed/32116556
http://dx.doi.org/10.3389/fncel.2020.00009
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