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Analysis of the interaction between metabotrophic and ionotrophic glutamate receptors in schizophrenia At the glutamatergic synapse both metabotrophic (mGluRs) G-protein coupled and ionotropic, channel gaited AMPA, kainate and NMDA) receptors are expressed. These different glutamate receptors are connected through a dense molecular network in the intracellular postsynaptic density (PSD). This intrigate molecular network provide a coordinated intracellular signaling response to glutamate. PSD-95, which is a prominent molecule of the PSD, provide connection to yet other molecules that connect to other types of glutamate receptors. So far little is known about the exact functional role of the interactions between ionotrophic and metabotrophic glutamate receptors and whether this connection is compromised in schizophrenia. Besides PSD-95 the molecules involved in connecting NMDA receptors with mGluRs in the membrane are GKAP and SHANK that both bind to PDZ domains of PSD-95 and Homer that connects SHANK with the mGluR receptor. In this project we have generated probes for these interacting proteins of the PSD and will analyse their expression by in-situ analysis. This project will provide information on the importance of abnormal interaction between NMDA and mGluRs in the pathology of schizophrenia.
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