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Differential expression of the GABA transporters GAT-1 and GAT-3 in brains of rats, cats, monkeys and humans

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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.

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Author notes

  1. David V. Pow

    Present address: Department of Anatomy, School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, 2308, Australia

Authors and Affiliations

  1. Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia

    David V. Pow, Robert K. P. Sullivan & Susan M. Williams

  2. Department of Anatomy, School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, 2308, Australia

    Robert K. P. Sullivan & Susan M. Williams

  3. Department of Biochemistry, School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Australia

    Heather L. Scott & Peter R. Dodd

  4. Howard Florey Institute, University of Melbourne, Parkville, Victoria, 3010, Australia

    David Finkelstein

Authors
  1. David V. Pow
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  2. Robert K. P. Sullivan
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  3. Susan M. Williams
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  4. Heather L. Scott
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  5. Peter R. Dodd
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  6. David Finkelstein
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Correspondence to David V. Pow.

Additional information

Grant support was provided by the National Health and Medical Research Council (Australia) grant nos. 210127 and 102448, and a Senior Research Fellowship to David Pow.

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Pow, D.V., Sullivan, R.K.P., Williams, S.M. et al. Differential expression of the GABA transporters GAT-1 and GAT-3 in brains of rats, cats, monkeys and humans. Cell Tissue Res 320, 379–392 (2005). https://doi.org/10.1007/s00441-004-0928-0

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  • DOI: https://doi.org/10.1007/s00441-004-0928-0

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