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Striatal expression of transcripts for NMDA associated PSD proteins in schizophrenia, major depression and bipolar disorder Work from our laboratory has previously identified abnormal expression of transcripts for several NMDA related PSD proteins in the thalamus as well as in cortical regions of subjects with schizophrenia. The changes in intracellular postsynaptic proteins have generally proven to be more solid than those of their corresponding receptor subunits indicating that the primary abnormality of the glutamatergic component in schizophrenia lies within the intracellular signaling machinery rather than in the receptor itself. In higher vertebrates the striatum, which is an integral part of the basal ganglia, receives strong corticostriatal afferent glutamatergic projections and has inhibitory GABAergic connections to the thalamus which in turn projects to the cortex. The circuitry of the basal ganglia with the thalamus and the cortex therefore intimately depends on functional excitatory and inhibitory striatal projections. Although a previous study of glutamate receptor subunit transcript expression and receptor binding identified only minor changes in the human striatum, we speculate that the NMDA related PSD molecules might still be abnormally expressed in schizophrenia and mood disorders as similar findings have been described for the thalamus.In this project we have analyzed striatal expression of transcripts for the NFL, PSD93, PSD95 and SAP102 NMDA related PSD proteins in schizophrenia. These experiments have associated significantly decreased expression of several of these key NMDA related signaling molecules in the human striatum with mental illnesses.
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