Postmortem Brain Tissue Examination in Neuropsychiatric

$0Z01FY2006MHNIH

National Institute Of Mental Health

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Abstract

The section collected 44 brains which were donated in the course of the last year.[unreadable] [unreadable] There are five areas of research for this protocol, as follows: 1. studies of susceptibility genes and related genes for schizophrenia relative to normal controls primarily in dorsolateral prefrontal cortex (DLPFC) and hippocampus; 2. studies of the effects of allelic variations in susceptibility genes on expression patterns of these same genes and related genes in DLPFC and hippocampus; 3. studies of normal human brain development; 4. studies of substance abuse and affective disorders; and 5. studies of animal models of schizophrenia. [unreadable] [unreadable] Findings from studies of susceptibility genes and related genes for schizophrenia: 1. decreased mRNA expression of glutamic acid decarboxylase (GAD1) in schizophrenics relative to controls in DLPFC; 2. increased mRNA expression in neuregulin (NRG1) in schizophrenics relative to controls in DLPFC; 3. decreased mRNA expression in binding partners of DISC1 (FEZ, LIS and NUDEL) in schizophrenics relative to controls in DLPFC and hippocampus. [unreadable] [unreadable] Findings from studies of the effects of allelic variations in susceptibility genes on the expression patterns of these same genes and related genes in human brain: 1. Allelic variations in GAD1 effect mRNA expression of GAD1 in DLPFC; 2. allelic variations in NRG1 that are part of a haplotype effect mRNA expression of type I and type IV isoforms of NRG1 in hippocampus; and 3. allelic variations in DISC1 effect mRNA expression of DISC1 binding partners including FEZ, LIS and NUDEL; and 3. identified and validated premortem and postmortem factors confounding the reliability of gene expression data and gene expression study designs.[unreadable] [unreadable] Findings from studies on normal human brain development across the lifespan: 1. found a reduction in the density or function of cholinergic interneurons in the striatum of schizophrenic brains relative to the control group and 2. hippocampal synaptic deficits in schizophrenia are indicative of a neurodevelopment abnormality during early synaptogenesis.[unreadable] [unreadable] Lastly, we are continuing our studies of substance abuse including cocaine and marijuana in conjunction with our NIDA collaborators and our animal model studies.

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