title: GAT-1 mediated GABA uptake in rat oligodendrocytes.
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.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, 60026, Italy.|Center for Neurobiology of Aging, INRCA IRCCS, Ancona, 60121, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Fattorini
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, 60026, Italy.|Center for Neurobiology of Aging, INRCA IRCCS, Ancona, 60121, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Melone
authors.affiliation: Achucarro Basque Center for Neuroscience, CIBERNED, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, 48940, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Sánchez-Gómez
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México.
authors.forename: Rogelio O
authors.initials: RO
authors.lastname: Arellano
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, 60026, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bassi
authors.affiliation: Achucarro Basque Center for Neuroscience, CIBERNED, and Departamento de Neurociencias, Universidad del País Vasco, Leioa, 48940, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Matute
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, 60026, Italy.|Center for Neurobiology of Aging, INRCA IRCCS, Ancona, 60121, Italy.|Fondazione di Medicina Molecolare, Università Politecnica delle Marche, Ancona, 60026, Italy.
authors.forename: Fiorenzo
authors.identifier: 0000-0001-5853-1566
authors.initials: F
authors.lastname: Conti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009900:Optic Nerve / Q000166:cytology; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000078308:Tiagabine; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D050485:GABA Plasma Membrane Transport Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D011509:Proteoglycans; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D012964:Sodium; D000078308:Tiagabine; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: GABA; GABA transporter 1; oligodendrocytes