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Cortical expression of NMDA receptor subunits and PSD proteins in schizophrenia Cortical dysfunction, especially of the prefrontal cortex, has been related to schizophrenia both on the cognitive and molecular levels. We have previously found abnormalities of the molecules involved in glutamatergic signaling in several subcortical structures including the thalamus, the hippocampus and in the striatum. Since all of these structures either directly or indirectly project back to specific areas of the prefrontal cortex we have compared cortical expression of transcripts for the NMDA related PSD molecules NFL, PSD93, PSD95 and SAP-102 in tissue from postmortem patients with schizophrenia or controls. In this study we have identified increased expression of transcripts for PSD93, PSD95 and NFL specifically related to either dorsal-lateral prefrontal cortex (dlPFC) or in a section corresponding to the anterior cingulate cortex (ACC). It is plausible that differences in transcript levels might be secondary to changes downstream of transcription such as protein synthesis, molecular stability and protein degradation. Since cellular function is determined not by the mRNA products but rather depends on the synthesized protein we have furthermore in this project analyzed protein expression of NMDA related receptor subunits and intracellular PSD proteins in the dlPFC and in the ACC. Interestingly we find corresponding to opposite changes in the protein expression as compared to transcript levels. As previously observed in other brain regions the changes of NMDA receptor subunits are relatively minor and unspecific. These findings indicate that biological processes downstream of transcription could be the primary cause of abnormal glutamatergic signaling in mental illnesses including schizophrenia.
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