Stressed-out mice offer clues to depression, anxiety, anorexia

EDITORS: Color photographs of mice in the experimental maze are available on request.

ANN ARBOR---Stressed-out mice created at the University of Michigan Medical School are helping scientists understand how a hormone that triggers the body's fight-or-flight response to stress also may be involved in depression, anxiety disorders and anorexia.

U-M scientists created the new mouse strain by deleting a gene that controls production of one protein. This protein binds to corticotropin-releasing hormone or CRH, a key neuroregulatory hormone produced by all mammals under stress. Binding prevents CRH from activating receptors that trigger the release of other stress hormones, as well as changes in metabolism and behavior.

Male mice without the gene for CRH-binding protein gained less weight and showed more anxiety-like behavior than littermates that could produce the protein.

"These mice exhibit anxiety-like behavior all the time---not just in response to an external stressor," says Audrey F. Seasholtz, Ph.D., a senior associate research scientist in the U-M's Mental Health Research Institute and an associate professor of biological chemistry in the U-M Medical School.

The initial U-M study documenting behavioral changes in mice without CRH-binding protein will be published in the Sept. 28 issue of the Proceedings of the National Academy of Sciences.

In the study, Seasholtz and her U-M colleagues used standard tests to document levels of stress hormones and anxiety-like behavior in mice without the gene for CRH-binding protein and compare them to test results in normal littermate controls.

Even though they were housed together and given identical access to food and water, male mice without the CRH-BP gene gained less weight between 7-9 weeks of age than did male control mice. Weight gain differences between experimental males and controls became even more significant from 10 to 15 week

Contact: Sally Pobojewski
University of Michigan

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