Previous studies from this laboratory have characterized the mRNA expression levels of the N-methyl-D-aspartic acid (NMDA) receptor subunits and NMDA receptor - associated PSD molecules in human thalamic nuclei and have found that there are changes in the mRNA expression levels of certain NMDA receptor subunits and NMDA receptor - associated PSD molecules in human thalamic nuclei in postmortem brain tissue from individuals with schizophrenia. For example, recent in situ hybridization studies have found that the NMDA receptor NR1 and NR2C subunit mRNAs are expressed at lower levels, whereas the NMDA receptor-associated PSD protein NFL, PSD93 and SAP102 mRNAs are expressed at higher levels in postmortem thalamus of human individuals with schizophrenia as compared to normal human individuals from a Mount Sinai Medical Center Brain Bank. Another brain region that is believed to have an important role in schizophrenia is the hippocampus and changes in NMDA receptor expression in hippocampus have been found in schizophrenia.

The overall goal of this project will be to determine the expression levels of the NMDA receptor subunits NR1, NR2A, NR2B, NR2C, NR2D and NMDA receptor-associated PSD proteins NFL, PSD93, PSD95 and SAP102 in hippocampal structures from postmortem human brains of schizophrenic, bipolar and control psychiatrically healthy individuals from an Australian brain bank. For this purpose we will use an in situ hybridization method using riboprobes radioalabelled with 35S that has already been developed and used in this laboratory.

These studies will expand our understanding of the molecular changes in schizophrenic brain associated with glutamatergic neurotransmission and possibly identify rational therapeutic targets.

Rob McCullumsmith