DECREASED EXPRESSION OF MESSENGER-RNAS ENCODING NON-NMDA GLUTAMATE RECEPTORS GLUR1 AND GLUR2 IN MEDIAL TEMPORAL-LOBE NEURONS IN SCHIZOPHRENIA

Schizophrenia is associated with a complex pattern of alterations in t he glutamatergic system of the brain. Previous studies have shown a re duced density of some hippocampal non-N-methyl-D-aspartate (non-NMDA) receptors which is accompanied by a loss of encoding receptor mRNA. We have extended this work using in situ hybridization histochemistry wi th oligonucleotide probes specific for two non-NMDA receptor transcrip ts, GluR1 and GluR2, in right and left medial temporal lobe sections f rom 9 schizophrenics and 14 matched normal controls. Both mRNAs were f ound to be decreased bilaterally and to a similar degree in the hippoc ampal formation in schizophrenia. Analysis of autoradiograms showed a regional loss of GIuR1 and GluR2 mRNAs in dentate gyrus, CA4, CA3 and subiculum. GluR2 mRNA was also reduced in parahippocampal gyrus. These reductions ranged from 25% to 70% in terms of S-35 nCi/g tissue equiv alents. Additionally we measured grain density for the mRNAs over indi vidual pyramidal neurons in each area. GluR1 and GluR2 mRNAs were less abundant per neuron in CA4 and CA3 in schizophrenia than in controls. GluR2 mRNA was also reduced significantly in parahippocampal gyrus ne urons, with an increase in the proportion of GluR1 mRNA to GluR2 mRNA in this cell population. No asymmetries in expression of GluR1 and Glu R2 were found in normal or schizophrenic brains. These data further th e evidence for reduced non-NMDA receptor expression in the medial temp oral lobe in schizophrenia. They confirm the decrease in GluR1 mRNA an d show that there are similar losses of GluR2 mRNA in the hippocampal formation. The pattern of changes in the two mRNAs suggests a common m echanism which is unknown but which may be a correlate of the neurodev elopmental abnormalities postulated to underlie the disease. The reduc tion of GluR2 mRNA but not GluR1 mRNA in parahippocampal gyrus neurons in schizophrenia may have functional consequences given the calcium p ermeability of non-NMDA receptors lacking the GluR2 subunit.