Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Altering a protein makes mice less fearful

03.08.2007
A University of Iowa study shows that loss or chemical inhibition of a protein, known as acid sensing ion channel protein (ASIC1a), reduces innate fear behavior in lab animals, making normally timid mice relatively fearless. The findings might provide useful insight into anxiety disorders and may even point the way to a new therapeutic target.

For humans and other animals, some fears seem to be, in large part, instinctive and inborn rather than learned. For example, laboratory animals fear certain predators even though they have never been exposed to a predator. However, little is known about the brain mechanisms involved in innate fear responses.

The UI study, published in the scientific journal, Biological Psychiatry, and available online July 30, shows that disrupting the ASIC1a protein alters innate fear reactions in mice and suggests that this protein may be a critical component of the brain systems that underlie innate fear.

The UI team, led by John Wemmie, M.D., Ph.D., assistant professor of psychiatry in the Roy J. and Lucille A. Carver College of Medicine, focused on ASIC1a because earlier research from the lab had shown that the protein was important in learned fear.

... more about:
»ASIC1a »Channel »Ion »Predator »Wemmie »anxiety »innate

The new study examined the protein's role in innate fear by disrupting ASIC1a in mice and observing the effect on several well-studied innate fear behaviors.

Mice that lack the protein were significantly less fearful of open spaces, loud noises and predator odor than normal mice.

In the odor test, the researchers placed a beaker containing a fox-odor chemical in the mouse enclosure. Normal mice froze when they smelled the chemical and avoided the beaker. In contrast, mice lacking the ASIC1a protein showed a much-reduced freezing response and even climbed onto the beaker. The team showed that the loss of ASIC1a did not affect the mouse's sense of smell.

"These lab animals have never been exposed to a predator. The freezing response seems hardwired and intuitive," said Matthew Coryell, a UI graduate student in the Neurosciences Program and lead author of the study. "Disrupting the gene reduced unconditioned, innate fear in the mice."

In a second set of experiments, the team also showed that chemically inhibiting the ASIC1a protein in normal mice (using a component of tarantula venom) similarly blunted the innate fear response.

"Showing that pharmacologically blocking the channel reduces innate fear behavior, in theory, sets the stage for investigating whether therapies that block these ion channels in humans might be effective in anxiety disorders," said Wemmie, who also is a physician and researcher at the Veterans Affairs (VA) Iowa City Health Care System.

The UI team found that ASIC1a is concentrated in brain regions that are critical for fear behaviors and responses, including the amygdala and an area called the bed nucleus of the stria terminalis (BNST), which is thought to be particularly important for innate fear behaviors. The study also shows that mice without ASIC1a have altered neuronal activity in these fear circuit structures.

The researchers speculate that because the gene is localized to brain regions involved in fear, targeting the ASIC1a protein might have a more focused effect on anxiety with fewer side effects than existing treatments, which affect systems throughout the brain, not just those involved in the fear response.

"Current treatments for anxiety have problems such as risk of addiction, slow onset of action and other types of side effects that make people not want to take them," Wemmie explained. "If we could find something that was more specific, or even had a different set of side effects, that could be an advantage."

Although this study examined the effect of disrupting the ion channel in mice, the mouse gene is very similar to the human gene, and the ASIC1a is present in human brains, where it is found in the amygdala.

There are no known mutations of the ASIC1a gene linked to altered fearfulness, but the UI study raises the possibility that mutations or variations in the gene might be associated with heritability of, or predisposition for, neuroticisim, phobias and other anxiety traits in humans.

The UI team plans to determine the specific sites of action of ASIC1a in the brain, and focus on understanding the role of the ion channel in the amygdala. They also are interested in whether the protein is involved in other types of psychiatric illness.

"Anxiety and other psychiatric illnesses, such as depression, are closely related. Some anxiety treatments often are effective for depression and vice versa," Wemmie said. "This study raises that possibility that blocking this protein might be useful for depression as well as anxiety."

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu
http://www.healthcare.uiowa.edu/labs/welsh/JAWemmie.htm

Further reports about: ASIC1a Channel Ion Predator Wemmie anxiety innate

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>