Accumulating findings from our laboratory indicate that the excitatory glutamate neurocircuitry of specific brain areas is disturbed in mental illness such as schizophrenia and mood disorders. Recent unpublished findings from our laboratory indicate that cellular processes such as protein synthesis, transport and membrane trafficking of NMDA related molecules is compromised in schizophrenia. Fractionation of subcellular membranes such as of the endoplasmatic reticulum (ER), golgi and the postsynaptic density from human postmortem tissue has proven to be associated with great difficulty and high inter-compartmental contamination which is probably due to the relative long postmortem interval. Using a method not relying on ultra centrifugation we have now developed a technique that allows us to separate intact subcellular structures. In this project we will initially analyze expression of NMDA related proteins in the ER fraction. ER retention and/or degradation might explain molecular changes we have found to be associated with schizophrenia in whole tissue homogenates. With this and related projects it is our aim to identify abnormalities of cellular function in schizophrenia that are related to protein synthesis, trafficking and degradation of the proteins involved in glutamatergic neurotransmission.

 Lars V. Kristiansen