The temporal lobe, including the hippocampus, subiculum and entorhinal cortex (EC) is one of the primary brain regions associated with schizophrenia. EC is an integral component of the conduit through which information flows to the hippocampus, helping regulate cortical-hippocampal-subcortical interactions. Various abnormalities in Layer ll/lll stellate neurons of the EC have been described in neuropathologic studies of schizophrenia, including aberrant cytoarchitectural arrangement, smaller neuron size, decreased expression of the cytoskeletal protein MAP2, altered glutamatergic innervation and differential expression of a number of mRNAs including transcription factors, synaptic proteins, and ionotropic glutamate receptor subunits. The strategic location of the EC and the previously identified biological correlates in this region make the EC an excellent candidate for probing disease-related differences in gene expression associated with schizophrenia. Studies in post-mortem human tissue have identified alterations in gene expression in the EC and other brain regions; however, several issues remain to be investigated: 1) whole genome exploration of brain regions implicated in schizophrenia and 2) lack of discernment between expression profiles in target neuronal populations and changes occurring in other neuronal and non-neuronal populations, and 3) differentiation of gene expression profiles from schizophrenia versus profiles attributable to antipsychotic drug history in primate brain. To this end, we will use human post mortem tissue from the EC of schizophrenics and compare changes to bipolar disorder using the array collection from the Stanley Medical Research Foundation. This will be accomplished at the regional level and within Layer ll/lll and Layer V neurons in the EC. Additional studies will explore the defined changes in a cohort of schizophrenics from the UPENN brain bank. In addition, comparisons will be made between the human post-mortem tissue and tissue acquired from rhesus monkeys following six month antipsychotic administration. To date, the treatment regimen, necropsy and tissue harvesting have been completed with both fresh frozen and paraffin-embedded EC available.
