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Mice with depression-like behaviors reveal possible source of human depression

St. Louis, Dec. 27, 2004 -- Mice missing a specific protein from their brains react to stress differently. The genetically engineered mice develop an imbalance in a hormone involved in stress responses, and during stressful situations, they behave as if they are depressed. Genetic variations in the same protein may be a significant cause of human depression, according to researchers at Washington University School of Medicine in St. Louis.

Their report will be published in the Proceedings of the National Academy of Sciences, appearing on-line at the journal's website during the week of Dec. 27 to 31, 2004 and in an upcoming print issue.

"A major obstacle to understanding depression has been finding what triggers its onset," says Maureen Boyle, predoctoral fellow and first author of the report. "We felt it was important to look at elements that regulate the body's stress system."

In response to stress, the brain signals the adrenal gland to release hormones, including glucocorticoid, a hormone that preserves physiological equilibrium in many organs. Because proper levels of glucocorticoid are important for normal function, the brain closely monitors and regulates the hormone.

People with major depressive disorder release excessive amounts of adrenal hormones, including glucocorticoid, possibly because their brains sense stress differently, according to the researchers.

"We wanted to find out if depression stems directly from the inability to sense glucocorticoid in the brain," says senior author Louis Muglia, Ph.D., associate professor of pediatrics, of molecular biology and pharmacology and of obstetrics and gynecology. "To test this, we developed an animal model that would tell us if changes in glucocorticoid receptor function could impart the animal equivalent of depression."

The researchers engineered mice that lose glucocorticoid receptors from their forebrains, specifically from the cortex and hippocampus, beginn
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Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
27-Dec-2004


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