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Why symptoms of schizophrenia emerge in young adulthood
Date:2/25/2010

Study leader Akira Sawa, M.D., Ph.D., professor of psychiatry and director of the program in molecular psychiatry at the Johns Hopkins University School of Medicine, says it is becoming clear that having a defective DISC1 gene might lead to an abnormally small number and size of dendritic spines, which could lead nerve cells to maintain weaker connections with unusually low numbers of neighboring neurons. Such abnormal connectivity has long been seen in autopsied brains from schizophrenia patients.

"Connections between neurons are constantly being made and broken throughout life, with a massive amount of broken connections, or 'pruning,' happening in adolescence," Sawa says. "If this pruning doesn't happen correctly, it may be one reason for the pathogenesis of schizophrenia," he adds.

In the second study, published in the Feb. 25 issue of Neuron, Sawa's team generated a new animal model of schizophrenia by temporarily shutting off the DISC1 gene in mice in the prefrontal cortex, a brain area known to differ in schizophrenic people. The new model allowed them to study other roles for DISC1 in the brain.

The researchers created their novel model by, again, using RNA interference. They injected short pieces of the nucleic acid RNA engineered to shut off the DISC1 gene into cavities in the developing brains of mouse fetuses two weeks after conception. Tests showed that these snippets of RNA migrated into cells in the prefrontal cortex, part of the brain located near the forehead.

This shutoff was temporary, with the gene's function fully restored within three weeks, or about a couple of weeks after birth. At various times after the gene was reactivated, the scientists examined the animals' brains and behavior, looking for differences from normal mice.

Sawa's team found that in the DISC1 shutoff group, nerve cells in the prefrontal cortex that produce dopamine, one of the chemical signals that nerve cells u
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Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

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