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Analysis of NMDA related trafficking molecules in schizophrenia Intracellular trafficking of the molecules involved in glutamate signaling from the cell body to the postsynaptic spine, is a prerequisite for functional neurotransmission. Published and unpublished data from our laboratory demonstrate that the overall expression of NMDA receptor subunits, both on the transcriptional and translational levels, is unaltered in schizophrenia and that the primary changes occur in the molecules of the postsynaptic density (PSD). However, correct function of the NMDA receptor requires that it is transported from the cytoplamic endoplasmatic reticulum along the dendritic spine to the postsynaptic density. If this transport of newly synthesized receptor protein is failing due to changes in transporting proteins NMDA receptor function would be seriously compromised. Trafficking of newly synthesized NMDA receptor from the ER to the cell membrane of the PSD is therefore a potential cellular aspect that might be compromised in schizophrenia. In this project we are making probes for several of the proteins that are known to be involved in NMDA trafficking and will test by in-situ analysis the transcriptional expression of these molecules in tissue from schizophrenic patients and control subjects. Thus, this project should provide a first pass analysis of a potential abnormal trafficking of glutamate receptors in schizoprenia.
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