GluR(5,6,7) subunit immunoreactivity on apical pyramidal cell dendrites inhippocampus of schizophrenics and manic depressives

Recent postmortem studies have suggested that changes in the regulation of kainate-sensitive glutamate receptors (kainate receptors) in the hippocampu s may play a role in schizophrenia. To explore this possibility further, th e distribution of immunoreactivity (IR) for the GluR(5,6,7) Subunits of the KR was assessed in a cohort consisting of 15 normal controls, 15 schizophr enics, and 9 manic depressives matched for age and postmortem interval (PMI ). Cross sections of hippocampus showed abundant GluR(5,6,7)-IR on apical d endrites of pyramidal neurons in the stratum radiatum and stratum molecular e. in normal controls, both the numerical and length density of IR dendrite s were much higher in sector CA2 than in sectors CA3 or CAI. When data for the individual groups were separately examined, the schizophrenics showed a 30-35% reduction in the density of GluR(5,6,7)-IR dendrites found in both stratum radiatum and stratum molecular of sectors CA3 and CA2, as well as p roximal and middle portions of CAI. In CA2, the magnitude of this decrease in schizophrenia was 2.5 times larger than that seen in any of the other se ctors. For the manic depressive group, no significant differences were obse rved in any sectors or laminae examined. The potential confounding effects of either age, PMI, or neuroleptic exposure do not explain the reduced dens ity of IR dendrites detected in the schizophrenic group. Taken together, th e preferential reduction of GluR(5,6,7)-IR observed, on apical dendrites of pyramidal neurons is consistent with a functional downregulation of the ka inate receptor in the hippocampus of schizophrenic brain. (C) 2001 Wiley-Li ss, Inc.