Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain.
Recent postmortem studies have reported a marked upregulation of GABAA receptor binding activity in the anterior cingulate and prefrontal cortices of schizophrenic subjects. Because the hippocampal formation is a key corticolimbic region that has also been implicated by both postmortem and brain imaging studies in the pathophysiology of this disorder, the current report has sought to determine whether alterations of GABAA receptor binding might also be detected in this region from 15 normal controls and 8 schizophrenic subjects. Using a low resolution autoradiographic approach, the results show a significant increase of specific GABAA receptor binding activity in the area dentata (granule cell layer), CA4, CA3 (str. oriens, str. pyramidale), subiculum, and presubiculum of the schizophrenic group. The magnitude of the increase was greatest in CA3 and lowest in the CA1 sector. When high resolution analyses were performed on emulsion-coverslip preparations, a modest increase of binding (43%, P = 0.05) was observed on pyramidal, but not non-pyramidal neurons in sector CA1. Rather unexpectedly, GABAA binding in sector CA3 was not significantly different on pyramidal cells, but was almost three-fold higher (P = 0.015) on non-pyramidal neurons of the schizophrenic group. There was no relationship of age or the postmortem interval to the parameters showing significant changes in the schizophrenic group. Moreover, patients both with and without neuroleptic exposure showed upregulation of GABAA receptor binding activity. Taking together the rather modest increase of binding activity in CA1 and the more marked upregulation in CA3, as well as the differential changes on pyramidal neurons of CA1 vs. non-pyramidal neurons in CA3, the findings reported here are consistent with the possibility that a disturbance of brain development could have occurred either perinatally or perhaps even well into the postnatal period, and have given rise to discreet subregional and cellular alterations of disinhibitory GABAergic modulation in sector CA3 of schizophrenics. Overall, the data reported here provide further evidence that alterations of GABAergic activity may occur in the hippocampal formation of schizophrenic patients.
Benes
F M
FM
Laboratory for Structural Neuroscience, McLean Hospital, Belmont, Massachusetts, USA.
Khan
Y
Y
Vincent
S L
SL
Wickramasinghe
R
R
D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D017966:Pyramidal Cells / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
D011963:Receptors, GABA-A