title: Differential expression of the GABA transporters GAT-1 and GAT-3 in brains of rats, cats, monkeys and humans.
abstract: The homeostasis of GABA is critical to normal brain function. Extracellular levels of GABA are regulated mainly by plasmalemmal gamma-aminobutyric acid (GABA) transporters. Whereas the expression of GABA transporters has been extensively studied in rodents, validation of this data in other species, including humans, has been limited. As this information is crucial for our understanding of therapeutic options in human diseases such as epilepsy, we have compared, by immunocytochemistry, the distributions of the GABA transporters GAT-1 and GAT-3 in rats, cats, monkeys and humans. We demonstrate subtle differences between the results reported in the literature and our results, such as the predominance of GAT-1 labelling in neurons rather than astrocytes in the rat cortex. We note that the optimal localisation of GAT-1 in cats, monkeys and humans requires the use of an antibody against the human sequence carboxyl terminal region of GAT-1 rather than against the slightly different rat sequence. We demonstrate that GAT-3 is localised mainly to astrocytes in hindbrain and midbrain regions of rat brains. However, in species such as cats, monkeys and humans, additional strong immunolabelling of oligodendrocytes has also been observed. We suggest that differences in GAT distribution, especially the expression of GAT-3 by oligodendrocytes in humans, must be accommodated in extrapolating rodent models of GABA homeostasis to humans.
authors.affiliation: Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia. d.pow@eaats.org
authors.forename: David V
authors.initials: DV
authors.lastname: Pow
authors.forename: Robert K P
authors.initials: RK
authors.lastname: Sullivan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Williams
authors.forename: Heather L
authors.initials: HL
authors.lastname: Scott
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dodd
authors.forename: David
authors.initials: D
authors.lastname: Finkelstein
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002144:Callithrix; D002415:Cats; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D000882:Haplorhini; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D013045:Species Specificity
chemical_list: D050485:GABA Plasma Membrane Transport Proteins