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

Cell Tissue Res (2005) 320: 379392

DOI 10.1007/s00441-004-0928-0REGULAR ARTICLEDavid V. Pow . Robert K. P. Sullivan .Susan M. Williams . Heather L. Scott . Peter R. Dodd .

David FinkelsteinDifferential expression of the GABA transporters GAT-1 and GAT-3

in brains of rats, cats, monkeys and humansReceived: 1 April 2004 / Accepted: 25 May 2004 / Published online: 9 April 2005

# Springer-Verlag 2005Abstract 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.Keywords Antibody . Astrocyte . Inhibitory .

Neurotransmitter . Oligodendrocyte . Rat . Cat . HumanGrant 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.D. V. Pow . R. K. P. Sullivan . S. M. Williams

Department of Physiology and Pharmacology,

School of Biomedical Sciences, University of Queensland,

Brisbane, 4072, AustraliaD. V. Pow (*) . R. K. P. Sullivan . S. M. Williams

Department of Anatomy, School of Biomedical Sciences,

University of Newcastle,Newcastle, NSW, 2308, Australiae-mail: [email protected]. L. Scott . P. R. DoddDepartment of...