Myelin Gene Products in Post Mortem Tissue

$0P50FY2002MHNIH

Mount Sinai School Of Medicine Of Nyu, New York NY

Investigators

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Abstract

DESCRIPTION (provided by applicant): We have carried out microarray analyses in a well-defined schizophrenic cohort provided by the Brain Bank Core (Core C). We observed that there were significant decreases in the levels of expression of six myelin/oligodendrocyte-related genes. In addition, we observed that making use of the expression levels of these 6 genes and 29 additional myelin/oligodendrocyte-related genes, we could perfectly discriminate the schizophrenics from controls. This observation implicates myelin/oligodendrocyte abnormalities in schizophrenia, and is further supported by the imaging studies (Project 4, DTI/MTI; Project 5, MRS) and neuroanatomical studies (Project 1, Oligodendroglia) detailed elsewhere in the proposal. The overarching aims of the current project are to expand on our existing results by determining the generality of the decreased myelin/oligodendrocyte related gene expression in the prefrontal cortex of schizophrenics to other prominently implicated brain regions and other schizophrenia cohorts, as well as to begin to understand the mechanisms underlying the decreased gene expression. These general aims and hypotheses will be tested by the following specific aims. Specific Aim 1: Examine the expression levels of myelin/oligodendrocyte-related genes in additional brain areas. Specific Aim 2: Study the expression levels of myelin/oligodendrocyte-related genes in additional patient samples. Specific Aim 3: Determine the cellular basis for altered gene expression. Specific Aim 4: Determine the molecular basis for altered gene expression.

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