DISTRIBUTION OF KAINATE RECEPTOR SUBUNIT MESSENGER-RNAS IN HUMAN HIPPOCAMPUS, NEOCORTEX AND CEREBELLUM, AND BILATERAL REDUCTION OF HIPPOCAMPAL GLUR6 AND KA2 TRANSCRIPTS IN SCHIZOPHRENIA

The mRNAs encoding kainic acid (KA) preferring glutamate receptor subu nits (GluR5-7, KA1 and KA2) are differentially expressed in rat brain. We have used regional and cellular in situ hybridization histochemist ry with subunit-specific S-35-labelled oligodeoxyribonucleotides to ex amine these mRNAs in adult human hippocampus, neocortex and cerebellum . GluR5 mRNA was detected only in Purkinje cells and a few scattered h ippocampal neurons. GluR6 mRNA was relatively abundant in all areas, n otably in dentate gyrus, pyramidal neurons of CA3, and cerebellar gran ule cells, as well as being present in superficial and deep laminae of the neocortex. Moderate signal for GluR7 mRNA was seen in deep lamina e of the neocortex with a weak signal in the dentate gyrus; in dipped sections GluR7 mRNA was also apparent over some pyramidal and non-pyra midal cells in hippocampus and over putative cerebellar stellate/baske t cells. KA1 mRNA was detected in the dentate gyrus but not reliably e lsewhere. The expression profile and abundance of KA2 mRNA was similar to that of GluR6 mRNA. For all five transcripts, concurrent hybridiza tion of rat brain sections produced the anticipated distribution of si gnal. The data indicate that the regional and cellular distribution of KA receptor subunit mRNAs in human hippocampus, neocortex and cerebel lum largely parallels that in the corresponding areas of rat brain, al beit at lower levels, especially with regard to GluR5 and KA1 transcri pts. In schizophrenia there is a partial loss of hippocampal non-NMDA receptors, but there are no data concerning KA receptor subunit expres sion. KA2 and GluR6 mRNAs were sufficiently abundant for a comparison in the left and right hippocampus between 11 schizophrenics and 13 con trols. Using film autoradiography, both mRNAs were significantly reduc ed in the schizophrenics, having controlled for the effects of brain p H, post mortem interval and age. GluR6 mRNA was also quantitated in ce rebellum, wherein no differences were found between cases and controls . In conjunction with earlier findings of reduced hippocampal GluR1 an d GluR2 expression and a loss of [H-3]KA binding sites, these data sho w that schizophrenia is associated with impaired expression of both AM PA- and KA-preferring ionotropic glutamate receptors. These deficits a re likely to contribute to the glutamatergic component of the disease pathophysiology. (C) 1997 Elsevier Science B.V.