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Brain circuit problem likely sets stage for the 'voices' that are symptom of schizophrenia
Date:6/5/2014

eletion syndrome develop schizophrenia, making it one of the strongest risk factors for the disorder. DNA is the blueprint for life. Human DNA is organized into 23 pairs of chromosomes that are found in nearly every cell.

Earlier work from Zakharenko's laboratory linked one of the lost genes, Dgcr8, to brain changes in mice with the deletion syndrome that affect a structure important for learning and memory. They found evidence that the same mechanism was at work in patients with schizophrenia. Dgcr8 carries instructions for making small molecules called microRNAs that help regulate production of different proteins.

For this study, researchers used state-of-the-art tools to link the loss of Dgcr8 to changes that affect a different brain structure, the auditory thalamus. For decades antipsychotic drugs have been known to work by binding to a protein named the D2 dopamine receptor (Drd2). The binding blocks activity of the chemical messenger dopamine. Until now, however, how that quieted the "voices" of schizophrenia was unclear.

Working in mice with and without the 22q11 deletion, researchers showed that the strength of the nerve impulse from neurons in the auditory thalamus was reduced in mice with the deletion compared to normal mice. Electrical activity in other brain regions was not different.

Investigators showed that Drd2 levels were elevated in the auditory thalamus of mice with the deletion, but not in other brain regions. When researchers checked Drd2 levels in tissue from the same structure collected from 26 individuals with and without schizophrenia, scientists reported that protein levels were higher in patients with the disease.

As further evidence of Drd2's role in disrupting signals from the auditory thalamus, researchers tested neurons in the laboratory from different brain regions of mutant and normal mice by adding antipsychotic drugs haloperidol and clozapine. Those drugs work by targeting Drd2. Origina
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Contact: Carrie Strehlau
carrie.strehlau@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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