Hippocampal loss of the GABAA receptor alpha 1 subunit in patients with chronic pharmacoresistant epilepsies.
Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABAA receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the alpha 1 subunit of the GABAA receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABAA receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABAA receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABAA receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABAA receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.
Department of Neuropathology, University of Bonn Medical Center, Germany.
H K
HK
Wolf
M
M
Spänle
M B
MB
Müller
C E
CE
Elger
J
J
Schramm
O D
OD
Wiestler
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000502:physiology; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011963:Receptors, GABA-A / Q000378:metabolism*
D011963:Receptors, GABA-A