Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A genome wide search for genes underlying anxiety disorders turned up unexpected candidates

31.10.2005


Increasing the activity of two enzymes better known for their role in oxidative stress metabolism turns normally relaxed mice into "Nervous Nellies," according to research conducted at the Salk Institute for Biological Studies and reported in the early online edition of Nature.



Locally overexpressing either glyoxalase 1 or glutathione reductase 1 in mouse brains significantly increased anxiety in usually relaxed mice and made already jittery mice even more anxiety-ridden. Inhibition of glyoxalase 1 had the opposite effect.

"Currently, very little is known about the genes that predispose to psychiatric disease," says first author Iiris Hovatta, who was a postdoctoral research in Salk’s Laboratory of Genetics when the research was conducted. "All of the 17 genes that we identified are very good candidates for human anxiety disorders and most of them have never been associated with anxiety-related behavior before," she adds.


"This is a very exciting study where we can genetically interfere with the behavior outcome, emphasizing the genetic hard wiring of certain traits,’’ says Inder Verma, professor in the Laboratory for Genetics at the Salk Institute.

Out of the 17 candidates, the researchers focused on the most promising ones, glyoxalase 1 and glutathione reductase 1, since both enzymes belonged to the same metabolic pathway. In addition, a study by Turkish scientists had found elevated levels of oxidative stress markers in patients with severe anxiety disorders. "It might be that oxidative stress metabolism and anxiety levels are linked, although we do not know the exact mechanism at the moment," says Hovatta.

Like other complex psychiatric traits, fear and anxiety are influenced by many genes. There is no such thing as a single "fear" gene that lets anxiety spiral out of control when the gene’s regulation is disturbed, making it difficult to identify the genetic roots of anxiety disorders.

For their study, the scientists relied on inbred mouse strains that differ considerably in their natural anxiety levels. Just like in humans suffering from anxiety disorders, the sights and sounds of unfamiliar environments can trigger panic in mice with anxious dispositions, causing them to freeze in place. Unlike their more relaxed contemporaries, naturally nervous mice are not explorers and may seem wary of open spaces.

Instead of studying individual genes the researchers simultaneously assessed the activity patterns of about 10,000 genes in specific brain regions with the help of microarrays. This extensive scan allowed the researchers to pinpoint multiple genes whose expression levels differed in relaxed and anxiety-prone mice.

To increase the specificity of their microarray analysis, they looked in only specific brain areas that have been shown to play a role in anxiety and fear (the amygdala, bed nucleus of the stria terminalis, cingulate cortex, hippocampus, hypothalamus, central peri-aqueductal grey and pituitary gland).

"We were incredibly surprised since out of the entire genome only 17 genes were robustly correlated with anxiety levels across many different strains," says Carrolee Barlow, lead author of the study and an adjunct professor in the Laboratory of Genetics. "Almost half of them were enzymes and not neurotransmitters as one might expect."

In the past, scientists tried to correlate complex psychiatric diseases with different forms of the genes controlling neurotransmitters, the chemical messengers that brain cells use to shuttle outgoing signals to neighboring cells, and their receptors, albeit with limited success. "That’s why we chose an unbiased approach that didn’t limit us to neurotransmitters," explains Barlow.

Now, Hovatta wants to find out what relevance, if any, the identified genes have to human anxiety disorders. "It is really exciting to study neurobiology of anxiety in mice and to understand the molecular mechanisms behind the regulation of behavior, but I am mostly interested in trying to find genes that predispose humans to anxiety disorders and to perhaps in the future try to develop better treatment practices. We are still far away from that," she cautions, "but it is the long term goal of the project."

Researchers contributing to the study include first author Iiris Hovatta, formerly at the Salk Institute, now at National Public Health Institute in Helsinki Finland, research assistants Richard S. Tennant and Robert Helton, research fellows Robert A. Marr and Oded Singer, both in the Laboratory of Genetics at the Salk Institute, Jeffrey M. Redwine at Neurome Inc., Julie A. Ellison, formerly at the Salk, now at Helix Medical Communications, Eric E. Schadt at Rosetta Inpharmatics LLC, Inder Verma, professor in the Laboratory for Genetics at the Salk Institute, David J. Lockhart, co-principal investigator and visiting scholar at the Salk Institute, and Carrolee Barlow, at Braincells Inc.

Cathy Yarbrough | EurekAlert!
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht BigH1 -- The key histone for male fertility
14.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Guardians of the Gate
14.12.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>