Featured Research

from universities, journals, and other organizations

Mice With Depression-like Behaviors Reveal Possible Source Of Human Depression

Date:
January 17, 2005
Source:
Washington University School Of Medicine
Summary:
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.

Dec. 28, 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, beginning at about three weeks of age and continuing until they reach a 95 percent loss at six months. The team felt the gradual loss could simulate the time course typical for human development of depression, which commonly begins in late adolescence.

During several stress-related tests, four- and six-month-old engineered mice showed an increase in behaviors suggestive of depression. The receptor-deficient mice also showed less interest in pleasurable stimuli, drinking significantly less of a sugar water solution than normal mice.

The depression-like behaviors closely corresponded to physiological changes. Four- and six-month-old engineered mice had significantly higher blood levels of glucocorticoid than normal mice. While normal mice suppressed their production of glucocorticoid when given a synthetic substitute hormone, the engineered mice showed no change in glucocorticoid levels, demonstrating an impairment in their ability to properly regulate their stress response.

The abnormal regulation of glucocorticoid in the engineered mice indicates that glucocorticoid receptors in the cortex and hippocampus—forebrain regions associated with higher thought, memory and emotion—regulate adrenal hormone levels. This regulatory role for forebrain cells has not been previously proven.

"Our findings in mice lacking glucocorticoid receptors suggest that some people may have a genetic makeup that reacts to stressful experiences by turning down the activity of the glucocorticoid receptor gene," Muglia says. "This may initiate a process leading to depression."

Using the engineered mice, the researchers next will seek genes that interact with glucocorticoid receptors and investigate the mechanism of action of antidepressant drugs. The projects will provide a fuller understanding of the underlying causes of depression and could lead to the development of new, more effective antidepressants, according to Muglia.

Boyle MP, Brewer JA, Funatsu M, Wozniak DF, Tsien JZ, Izumi Y, Muglia LJ. Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proceedings of the National Academy of Sciences, January 2005.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Mice With Depression-like Behaviors Reveal Possible Source Of Human Depression." ScienceDaily. ScienceDaily, 17 January 2005. <www.sciencedaily.com/releases/2005/01/050110121737.htm>.
Washington University School Of Medicine. (2005, January 17). Mice With Depression-like Behaviors Reveal Possible Source Of Human Depression. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2005/01/050110121737.htm
Washington University School Of Medicine. "Mice With Depression-like Behaviors Reveal Possible Source Of Human Depression." ScienceDaily. www.sciencedaily.com/releases/2005/01/050110121737.htm (accessed October 2, 2014).

Share This



More Plants & Animals News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) — Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
Powered by NewsLook.com
Cultural Learning In Wild Chimps Observed For The First Time

Cultural Learning In Wild Chimps Observed For The First Time

Newsy (Oct. 1, 2014) — Cultural transmission — the passing of knowledge from one animal to another — has been caught on camera with chimps teaching other chimps. Video provided by Newsy
Powered by NewsLook.com
Earth Has Lost Half Its Vertebrate Wildlife Since 1970: WWF

Earth Has Lost Half Its Vertebrate Wildlife Since 1970: WWF

Newsy (Sep. 30, 2014) — A new study published by the World Wide Fund for Nature found that more than half of the world's wildlife population has declined since 1970. Video provided by Newsy
Powered by NewsLook.com
Annual Dog Surfing Competition Draws California Crowds

Annual Dog Surfing Competition Draws California Crowds

AFP (Sep. 30, 2014) — The best canine surfers gathered for Huntington Beach's annual dog surfing competition, "Surf City, Surf Dog." Duration: 01:15 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins