?s abstract): The goal of this project is to study the expression of the NR3 subunit of the NMDA receptor (NMDAR) in human fetal and adult schizophrenic brain. NMDAR?s play an important role in many normal and pathological processes in the brain. The NMDAR is a multimeric complex comprised of 4 or 5 subunits (NR1, NR2A-D and NR3) derived from six different genes. Since subunit composition can alter the pharmacological and physiological properties of the NMDAR, differential expression of these various subunits may reflect an important level of NMDAR regulation. Pharmacological studies suggest NMDAR dysfunction plays a role in schizophrenia and changes in NMDAR subunit expression have been reported in schizophrenia, supporting this hypothesis, although the NR3 subunit has not been studied in this illness. Prenatal insults to the brain during the second trimester of pregnancy have been linked to schizophrenia, suggesting a neurodevelopmental component may play a role in the etiology of schizophrenia. Studies in rodent suggest that the NR3 subunit is expressed at a time in development that may be relevant in schizophrenia. Further, electrophysiological studies demonstrate that incorporation of the NR3 subunit into a functional NMDAR can decrease NMDAR current, consistent with the glutamate hypothesis of schizophrenia involving decreased NMDAR activity. Thus, we hypothesize that the NR3 subunit may be important in the etiology and/or pathophysiology of schizophrenia. Since the human NR3 subunit has not been investigated, these studies are designed to 1) examine NR3 mRNA expression and protein levels in fetal and adult human brain, and 2) test the hypothesis that NR3 expression is altered in schizophrenia.
