IMMUNOAUTORADIOGRAPHIC EVIDENCE FOR A LOSS OF ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE-PREFERRING NON-N-METHYL-D-ASPARTATE GLUTAMATE RECEPTORS WITHIN THE MEDIAL TEMPORAL-LOBE IN SCHIZOPHRENIA

Decreased expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxacole propionate (AMPA)-preferring non-N-methyl-D-aspartate (non-NMDA) glut amate receptors (GluRs) occurs in the medial temporal lobe of schizoph renics in terms of reduced abundance of GluR1 and GluR2 subunit mRNAs. To investigate further these receptors in schizophrenia, we have perf ormed a quantitative immunoautoradiographic study in medial temporal l obe sections of II schizophrenics and 10 well-matched controls. GluR1 and GluR2/3 were detected with polyclonal antisera coupled to S-35-lab eled secondary antibodies. Both subunits were vulnerable to a prolonge d postmortem interval and poor agonal state as indicated by brain pH. GluR1 also tended to decline with increasing age. These factors were t herefore used as covariates. GluR1 abundance was reduced in schizophre nics in parahippocampal gyrus (p < .025). While GluR2/3 was lower in m ost subfields in the schizophrenics, significantly so in CA4 (p < .02) . The present data extend the evidence for decreased expression of the AMPA subtype of non-NMDA receptors in the medial temporal lobe in sch izophrenia, although the magnitude and spatial extent of the loss is s maller than that affecting the encoding mRNAs. Impaired AMPA receptor expression is consistent with a neurodevelopmental origin and with hyp otheses of glutamatergic hypofunction in the disease; however, ifs tru e pathophysiological significance and relationship to the other neurop athological and pathochemical abnormalities in the medial temporal lob e in schizophrenia remain to be determined. (C) 1997 Society of Biolog ical Psychiatry.