Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover anxiety and aggression gene in mice

23.01.2003


Opens new door to study of mood disorders in humans



Researchers report finding a gene that is essential for normal levels of anxiety and aggression. Calling it the Pet-1 gene, researchers at the Case Western Reserve University School of Medicine Department of Neurosciences say that when this gene is removed or "knocked out" in a mouse, aggression and anxiety in adults are greatly elevated compared to a control (also called wild type) mouse.

(Videos displaying aggressive behavior of Pet-1 knockout mice can be viewed at http://neurowww.cwru.edu/faculty/deneris.shtml; click Movies Link.)


Other neurologic functions, such as motor coordination, feeding, and locomotor activity, do not appear altered in the knockout mouse.

Anxiety and aggression are normal and important behaviors that allow individuals to respond appropriately to threats or cope with a challenging environment. However, it is clear that uncontrollable or excessive anxiety and aggression can be counterproductive.

"The behavior of Pet-1 knockout mice is strikingly reminiscent of some human psychiatric disorders that are characterized by heightened anxiety and violence," says Evan Deneris, Ph.D., principal investigator of the study and a neuroscientist at CWRU. The study is published in the Jan. 23 issue of the science journal Neuron.

Previously, Deneris’ lab showed that in the brain Pet-1 is active only in serotonin nerve cells or neurons, a relatively small number of cells (among the trillions of neurons in a human brain, only a few hundred thousand produce serotonin) that profoundly affect emotions. Serotonin is a chemical that acts as a messenger or neurotransmitter allowing neurons to communicate with one another in the brain and spinal cord. It is important for ensuring an appropriate level of anxiety and aggression. Defective serotonin neurons have been linked to excessive anxiety, impulsive violence, and depression in humans.

Antidepressant drugs such as Prozac and Zoloft work by increasing serotonin activity and are highly effective at treating many of these disorders. But it is unknown why some people have dysfunctional serotonin neurons and whether this can be caused by defects in genes that are normally required for their early development.

"We have now shown that Pet-1 is required specifically for fetal development of serotonin neurons," says Deneris. In mice missing this gene, most serotonin neurons fail to be generated in the fetus and the ones that remain are defective. This leads to very low serotonin levels throughout the developing brain, which in turn results in altered behavior in adults. "This is the first gene shown to impact adult emotional behavior through specific control of fetal serotonin neuron development."

Deneris and his colleagues employed sensitive tests of aggression and anxiety to compare the behavior of the knockout mice to wild type mice. One such aggression test measures a mouse’s response time to an intruder mouse entering its territory. The Pet-1 knockout mice attacked intruders much more quickly and more often than wild type mice. In fact, knockout mice often would not engage in normal exploratory behavior directed toward the intruder before attacking it. Excessive anxiety-like behavior was evident in another test, measuring the amount of time a mouse spends in open unprotected areas of a test chamber compared to closed protected areas. Unlike normal mice, which will enter and explore an unprotected portion of the test chamber, the Pet-1 knockout mice avoided this area all together, indicating abnormal anxiety-like behavior.

The human and mouse serotonin systems share many anatomical and functional features, and the same Pet-1 gene is present in the human genome. Therefore, Deneris’ discovery creates the first animal model for gaining a greater understanding of the causes of abnormal anxiety and aggression brought about through defective early serotonin neuron development. Deneris also sees this knockout mouse being used as a model for screening new drugs that can treat both aggression and anxiety. "If in fact particular genetic variants of Pet-1 are associated with excessive anxiety or violent activity in humans, then tests to detect these variants might be useful for early diagnosis of people who may be at risk for developing these abnormal behaviors," Deneris says. His lab plans more studies in mice to see how the gene affects sleep-wake patterns, learning and memory, and sexual behavior – all functions controlled in part by serotonin.


###
Lead authors on the study are Timothy J. Hendricks, and Dmitry V. Fyodorov, who were graduate students in Deneris’s lab at the time of the study. Other authors are, from CWRU: Lauren J. Wegman, Nadia B. Lelutiu, Elizabeth A. Pehek, Ph.D., Bryan Yamamoto, Ph.D., and Jerry Silver, Ph.D.; and, from Baylor College of Medicine, Edwin J. Weeber, Ph.D., and J. David Sweatt, Ph.D.


George Stamatis | EurekAlert!
Further information:
http://neurowww.cwru.edu/faculty/deneris.shtml
http://www.cwru.edu/

More articles from Life Sciences:

nachricht If Machines Could Smell ...
19.07.2019 | Fraunhofer-Institut für Produktionstechnik und Automatisierung IPA

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Heat flow through single molecules detected

19.07.2019 | Physics and Astronomy

Heat transport through single molecules

19.07.2019 | Physics and Astronomy

Welcome Committee for Comets

19.07.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>