GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus.
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.
Lee
Tih-Shih
TS
Department of Psychiatry, Yale University School of Medicine, Park Street, New Haven, CT 06520, USA.
Bjørnsen
Lars Petter
LP
Paz
Carlos
C
Kim
Jung H
JH
Spencer
Susan S
SS
Spencer
Dennis D
DD
Eid
Tore
T
de Lanerolle
Nihal C
NC
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D012598:Sclerosis
D050485:GABA Plasma Membrane Transport Proteins; C493413:SLC6A1 protein, human; C493416:SLC6A11 protein, human