Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

28.12.2004


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.

Jim Dryden | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NASA's AIM observes early noctilucent ice clouds over Antarctica

05.12.2016 | Earth Sciences

Shape matters when light meets atom

05.12.2016 | Physics and Astronomy

Researchers uncover protein-based “cancer signature”

05.12.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>