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GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus

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Abstract

The gamma amino butyric acid (GABA) transporters GAT-1 and GAT-3 were localized by immunohistochemistry in hippocampi removed for the control of medically intractable temporal lobe epilepsy (TLE). The study aimed to determine the relationship of GABA transporter expression to known patterns of hippocampal hyperexcitability and extracellular GABA levels. GAT-1 was localized in axon terminals and small neuronal cell bodies, and in non-sclerotic hippocampi was strongly expressed throughout all regions of the hippocampal formation. In the epileptogenic hippocampus exhibiting Ammon’s horn sclerosis, immunoreactivity was reduced in the sclerotic regions CA3 and CA1, and around the cell bodies of dentate granule cells, but was increased along granule cell dendrites. GAT-3 was weakly expressed, if at all, in non-sclerotic hippocampi, but more prominently expressed in sclerotic hippocampi. GAT-3 expression was confined to cells resembling protoplasmic astrocytes, which were located in regions of relative neuronal sparing such as the dentate gyrus and hilus of the sclerotic hippocampus. The reduction in GAT-1 around granule cells in the sclerotic hippocampus could explain the prolonged GABA responses in this region. The loss of GAT-1 (a marker of GABAergic terminals) would also suggest a reduced GABAergic input to the granule cells, thus facilitating hyperexcitability. The increased GAT-3 expression in astrocytes in regions of relative neuronal sparing in the sclerotic hippocampus may be related to the overall low levels of extracellular GABA observed in the sclerotic hippocampus and their increased excitability.

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Acknowledgments

We thank Ms. Ilona Kovacs for her excellent technical assistance with the immunohistochemistry. We are indebted to Professor N.C. Danbolt for providing us with GAT1 antibodies. Some of the data reported here was part of the Senior Thesis of Carlos Paz at Yale College.

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Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, Park Street, New Haven, CT, 06520, USA

    Tih-Shih Lee

  2. Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA

    Lars Petter Bjørnsen, Carlos Paz, Dennis D. Spencer, Tore Eid & Nihal C. de Lanerolle

  3. Department of Pathology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Jung H. Kim

  4. Department of Neurology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Susan S. Spencer

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  1. Tih-Shih Lee
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  2. Lars Petter Bjørnsen
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  3. Carlos Paz
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  4. Jung H. Kim
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  8. Nihal C. de Lanerolle
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Correspondence to Nihal C. de Lanerolle.

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Lee, TS., Bjørnsen, L.P., Paz, C. et al. GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus. Acta Neuropathol 111, 351–363 (2006). https://doi.org/10.1007/s00401-005-0017-9

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  • DOI: https://doi.org/10.1007/s00401-005-0017-9

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