Glutamate receptor expression in schizophrenic brain

Abstract

Glutamatergic dysfunction has been suggested as a possible substrate of the pathophysiology of schizophrenia. Of the multiple glutamate receptors, those most commonly implicated in schizophrenia are the ionotropic subtypes, the NMDA, AMPA, and kainate receptors. The expression of the glutamate receptors has been determined at multiple levels of gene expression in postmortem brain samples from schizophrenics and controls; while results have not been entirely consistent from study to study, several generalizations have emerged from this literature: (1) The AMPA receptor is abnormally decreased in expression in the schizophrenic hippocampus, involving decreased levels of subunit transcripts and protein levels, as well as binding sites, (2) similar changes are seen for kainate receptor expression in the hippocampus, and (3) the obligate NMDA receptor subunit, NMDAR1, may be abnormally expressed in some cortical regions in schizophrenia. These data support the hypothesis of abnormal glutamatergic neurotransmission involving the ionotropic glutamate receptors in schizophrenia. Copyright (C) 2000 Elsevier Science B.V.