Decreased Glutamic Acid Decarboxylase67 Messenger RNA Expression in a Subset of Prefrontal Cortical γ-Aminobutyric Acid Neurons in Subjects With Schizophrenia
Top Cited Papers
- 1 March 2000
- journal article
- research article
- Published by American Medical Association (AMA) in Archives of General Psychiatry
- Vol. 57 (3), 237-245
- https://doi.org/10.1001/archpsyc.57.3.237
Abstract
Background Markers of γ-aminobutyric acid (GABA) neurotransmission seem to be altered in the prefrontal cortex (PFC) of subjects with schizophrenia. We sought to determine whether the expression of the messenger RNA (mRNA) for the synthesizing enzyme of GABA, glutamic acid decarboxylase67 (GAD67), is decreased in the PFC of subjects with schizophrenia, whether this change is present in all or only some GABA neurons, and whether long-term treatment with haloperidol decanoate contributes to altered GAD67 mRNA expression. Methods Tissue sections from 10 pairs of subjects with schizophrenia and control subjects and 4 pairs of haloperidol-treated and control monkeys were processed for in situ hybridization histochemical analysis with sulfur-35–labeled oligonucleotide probes for GAD67 mRNA and exposed to nuclear emulsion. Within each layer of PFC area 9, neurons expressing a detectable level of GAD67 mRNA were quantified for cell density and the relative level of mRNA expression per cell (grain density per neuron). Results In subjects with schizophrenia, the density of labeled neurons was significantly (P<.05) decreased by 25% to 35% in cortical layers 3 to 5. In contrast, the mean grain density per labeled neuron did not differ across subject groups. Similar analyses in monkeys revealed no effect of long-term haloperidol treatment on either the density of the labeled neurons or the grain density per labeled neuron. Conclusions These findings indicate that in subjects with schizophrenia, GAD67 mRNA expression is relatively unaltered in most PFC GABA neurons but is reduced below a detectable level in a subset of GABA neurons. Altered GABA neurotransmission in this subset may contribute to PFC dysfunction in subjects with schizophrenia.Keywords
This publication has 36 references indexed in Scilit:
- A decrease of reelin expression as a putative vulnerability factor in schizophreniaProceedings of the National Academy of Sciences of the United States of America, 1998
- The sexually dimorphic nucleus of the hypothalamus contains GABA neurons in rat and manBrain Research, 1996
- Local circuit neurons of the prefrontal cortex in schizophrenia: selective increase in the density of calbindin-immunoreactive neuronsPsychiatry Research, 1995
- Neural Circuitry of the Prefrontal Cortex in SchizophreniaArchives of General Psychiatry, 1995
- Gene Expression for Glutamic Acid Decarboxylase Is Reduced Without Loss of Neurons in Prefrontal Cortex of SchizophrenicsArchives of General Psychiatry, 1995
- Regionally selective deficits in uptake sites for glutamate and gamma-aminobutyric acid in the basal ganglia in schizophreniaPsychiatry Research, 1992
- Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.Proceedings of the National Academy of Sciences of the United States of America, 1992
- Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenicsJournal of Neuroscience, 1992
- Evidence of glutamatergic deficiency in schizophreniaNeuroscience Letters, 1991
- Reduced GABA uptake sites in the temporal lobe in schizophreniaNeuroscience Letters, 1989