title: Distribution of glutamate decarboxylase65 immunoreactive puncta on pyramidal and nonpyramidal neurons in hippocampus of schizophrenic brain.
abstract: Recent studies have reported an increase in GABAA receptor binding activity in several key corticolimbic regions, including the hippocampal formation, of postmortem schizophrenic brain. Because this change has been postulated to represent a compensatory upregulation of this receptor, the current report has sought to determine whether a decrease of glutamate decarboxylase (GAD), the enzyme responsible for the synthesis of GABA, may also be present in the hippocampus of schizophrenic subjects. A standard immunoperoxidase technique, together with a computer-assisted microscopic analysis, has been employed to evaluate the distribution of the 65 kDalton isoform of GAD (GAD65) in 12 normal controls and 13 schizophrenic subjects matched for age and postmortem interval (PMI). The results show no significant difference in the density of GAD65-immunoreactive (-IR) puncta in contact with pyramidal neurons (PN), nonpyramidal neurons (NP), or neuropil (NPL) in sectors CA1-4 and their various sub-laminae. When the data were considered in relation to neuroleptic exposure, a significant positive correlation between the density of GAD65-IR puncta and drug dose was found on both PNs (r = 0.814, P = 0.002; r = 0.777, P = 0.005, respectively) and NPs (r = 0.673, P = 0.023; r = 0.672, P = 0.024, respectively) in sectors CA4 and CA3. A similar result was found in the stratum oriens of CA3 (r = 0.704, P = 0.016) and CA2 (r = 0.774, P = 0.009). In each instance, two neuroleptic free schizophrenics showed the lowest density of GAD65-IR puncta. There was no significant relationship between the density of GAD65-IR puncta with either age or PMI. Taken together with previous data showing an upregulation of GABAA receptor activity in sectors CA3 and CA2, particularly the stratum oriens, this study provides further evidence in support of the hypothesis that an intrinsic defect of GABAergic activity may occur in the hippocampal formation of schizophrenic patients and show dose-related increases in relation to neuroleptic exposure.
authors.affiliation: Laboratory for Structural Neuroscience, McLean Hospital, Belmont, Massachusetts 02178, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Todtenkopf
authors.forename: F M
authors.initials: FM
authors.lastname: Benes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology*; D017966:Pyramidal Cells / Q000201:enzymology*; D012559:Schizophrenia / Q000201:enzymology* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; D005968:Glutamate Decarboxylase