The section collected 68 brains which we donated in the course of the last year. There are five areas of research for this protocol, as follows: studies of susceptibility genes for schizophrenia relative to normal controls, studies of the effects of susceptibility genes on expression patterns of other genes in human brain, studies of normal human brain development, studies of cocaine abuse, and studies of animal models of schizophrenia. Findings from studies of susceptibility genes for schizophrenia: abnormalities in both dysbindin and neuregulin were found in the DLPFC of schizophrenic subjects relative to normal controls. Findings from studies of the effects of susceptibility genes on the expression patterns of other genes in human brain: COMT genotype associated with schizophrenia led to increased mRNA expression for tyrosine hydroxylase in midbrain, a mechanism that shows how a susceptibility gene for schizophrenia can lead to increased dopamine turnover, which is thought to increase the likelihood of psychosis. In addition, a number of other genes have been shown to be effected by other genotypes associated with schizophrenia susceptibility genes such as dysbindin and the metabotropic glutamate receptor-3. Findings of studies of normal human brain development focusing on the dorsolateral prefrontal cortex (DLPFC): a number of genes appear to have their maximum expression in adolescence or young adulthood, corresponding to the period of greatest vulnerability for the onset of schizophrenia, including D1 receptors, BDNF, and GAP-43. Synaptophysin mRNA decreases with advancing age. Surprisingly, protein expression for synaptophysin does not follow the same pattern of changes noted in mRNA expression for synaptophysin. Instead, its pattern is similar to the other mRNA species that peak in adolescence and young adulthood. These findings appear to be specific to DLPFC in contrast to the occipital lobe, which was studied as a control region of cortex. Lastly, NMDA receptor subunits (2B/2A ratio) were highest in neonates and infants in the mesial temporal lobe. Findgs from studies of brains from individuals who abused cocaine: cDNA microarray studies have identified a number of different expression patterns in subjects who abused cocaine in comparison to normal non-addicted controls, across several brain regions. Findings from studies of animal models of schizophrenia: an interesting animal model of schizophrenia has involved lesioning the neonatal ventral hippocampal formation of rats using tetrodotoxin.
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