Changes in GABA transporters in the rat hippocampus after kainate-induced neuronal injury: decrease in GAT-1 and GAT-3 but upregulation of betaine/GABA transporter BGT-1

The gamma-aminobutyric acid (GABA) transporters GAT-1, GAT-2, GAT-3, and BGT-1 have been cloned and identified according to their differential amino acid sequences and pharmacologic properties. In contrast to GAT-1, -2, or -3, BGT-1 is capable of utilizing both GABA and betaine as substrates. Betaine has been suggested to be a protective osmolyte in the brain. Because changes in expression of GABA transporters/BGT-1 might result in alterations in levels of GABA/betaine in the extracellular space, with consequent effects on neuronal excitability or osmolarity, the present study was carried out to explore expression of GABA transporters in the rat hippocampus after kainate-induced neuronal injury. A decrease in GAT-1 and GAT-3 immunostaining but no change in GAT-2 staining was observed in the degenerating CA subfields. In contrast, increased BGT-1 immunoreactivity was observed in astrocytes after kainate injection. BGT-1 is a weak transporter of GABA in comparison to other GABA transporters and the increased expression of BGT-1 in astrocytes might be a protective mechanism against increased osmotic stress known to occur after excitotoxic injury. On the other hand, excessive or prolonged BGT-1 expression might be a factor contributing to astrocytic swelling after brain injury.