GABABR1 receptor protein expression in human mesial temporal cortex: Changes in temporal lobe epilepsy

Abstract

Immunocytochemistry was used to examine γ-aminobutyric acid beta (GABA)BR1a-b protein expression in the human hippocampal formation (including dentate gyrus, hippocampus proper, subicular complex, and entorhinal cortex) and perirhinal cortex. Overall, GABABR1a-b immunostaining was intense and widespread but showed differential areal and laminar distributions of labeled cells. GABABR1a-b-immunoreactive (-ir) neurons were found in the three main layers of the dentate gyrus, the most intense labeling being present in the polymorphic layer, whereas the granule cells were moderately immunoreactive. Except for slight variations, similar distribution patterns of GABABR1a-b immunostaining were found along the different subfields of the Ammon's horn (CA1-CA4). The highest density of GABABRla-b-ir neurons was localized in the stratum pyramidale, where virtually every pyramidal cell was intensely immunoreactive, including the proximal part of the apical dendrites. Within the subicular complex, a more intense GABABRla-b immunostaining was found in the subiculum than in the presubiculum or parasubiculum, especially in the pyramidal and polymorphic cell layers. In the entorhinal cortex, distribution of GABABR1a-b immunoreactivity was localized mainly in both pyramidal and nonpyramidal cells of layers II, III, and VI and in the superficial part of layer V, with layers I, IV, and deep layer V being less intensely stained. In the perirhinal cortex, the most intense GABABR1a-b immunoreactivity was located in the deep part of layer III and in layer V and was mainly confined to medium-sized and large pyramidal cells. Thus, the differential expression, but widespread distribution, of GABABR1a-b protein found in the present study suggests the involvement of GABAB receptors in many circuits of the human hippocampal formation and adjacent cortical structures. Interestingly, the hippocampal. formation of epileptic patients (n = 8) with hippocampal sclerosis showed similar intensity of GABABR1a-b immunostaining in the surviving neurons located within or adjacent to those regions presenting neuronal loss than in the controls. However, surviving neurons in the granule cell layer of the dentate gyrus displayed a significant reduction in immunostaining in 7 of 8 patients. Therefore, alterations in inhibitory synaptic transmission through GABAB receptors appears to affect differentially certain hippocampal circuits in a population of epileptic patients. This reduction in GABABRla-b expression could contribute to the pathophysiology of temporal lobe epilepsy. © 2002 Wiley-Liss, Inc.