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Scientists demonstrate link between genetic defect and brain changes in schizophrenia
Date:10/16/2009

s" a scientific theory LaMantia calls the "Hail Mary" of schizophrenia pathologists.

For many years, researchers searched in vain for any indication that the brains of patients with schizophrenia were different from normal subjects --for some laboratory finding along the lines of the plaques and tangles characteristic of Alzheimer's disease or the degeneration of dopamine cells that are the calling card of Parkinson's disease. Similar degenerative change has never been identified for schizophrenia. Finally they proposed that the defects in schizophrenia must arise before the brain is fully formed, rather than after.

Then researchers began to discover regions of the genome -- many of which had neurodevelopmental functions -- that made people susceptible to schizophrenia.

In this study, LaMantia and his colleagues decided to pursue deletion of one such region on human chromosome 22, which causes DiGeorge syndrome in humans, because it is the single best-defined genetic lesion associated with schizophrenia. They tracked two subclasses of neural stem cells -- called basal and apical progenitors -- throughout early brain development in a mutant mouse with the same genetic deletion. They found that the basal progenitors divided more slowly than they should, and as a result the cells that they give rise to in the cortex were not generated in the proper numbers.

The researchers also looked at another population of cells, the GABAergic cells that are thought to essentially put the brakes on electrical activity in mature cortical circuits. The function of these cells is believed to be one of last processes to be disrupted in the schizophrenic brain. LaMantia found that these GABAergic neurons never made their way to their correct positions in the cortical layers of the brain of the mouse model of DiGeorge Syndrome .

The researchers would now like to figure out how these alterations in the circuitry of the brain affect the behavior
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Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert

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