51. Altered GABA transporter-1 mRNA expression in prefrontal cortical neurons in schizophrenia

Abstract

Within the prefrontal cortex (PFC) of schizophrenic subjects, recent studies suggest that alterations in markers of GABA neurotransmission, including decreased immunoreactivity for the GABA membrane transporter, GAT-1, may be most prominent in the chandelier cell subpopulation of GABA neurons (PNAS 95:5341, 1998). In order to explore one possible mechanism for these findings, we tested the hypothesis that GAT-1 mRNA expression is decreased in a subset of PFC GABA neurons in schizophrenia. Tissue sections containing PFC area 9 from 10 schizophrenic subjects, each matched to one control subject for sex, age, and postmortem interval, were processed for in situ hybridization histochemistry with S-labeled oligonucleotide probes for GAT-1 mRNA and exposed to nuclear emulsion. The density of labeled neurons was decreased in the schizophrenic subjects by 21–32% in layers 1–5 but was unchanged in layer 6. In contrast, mean grain density per labeled neuron, a relative measure of the cellular level of GAT-1 mRNA expression, did not differ between schizophrenic and control subjects. These findings indicate that GAT-1 mRNA expression is relatively unaltered in the majority of PFC GABA neurons in schizophrenic subjects, but is reduced below a detectable level in a subset of GABA neurons. Furthermore, the magnitude and laminar pattern of these results were strikingly similar to our previous study of GAD67 mRNA expression in the same subjects (Arch Gen Psych, in press). Thus, markers of both GABA synthesis and uptake appear to be altered at the level of gene expression in a subset of GABA neurons, and the resulting changes in GABA neurotransmission may contribute to PFC dysfunction in schizophrenia.