Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hulk smash? Maybe not anymore: scientists block excess aggression in mice

20.06.2012
Understanding the biological basis of violent outbursts in mice could lead to treatments for antisocial and aggressive behavior

Pathological rage can be blocked in mice, researchers have found, suggesting potential new treatments for severe aggression, a widespread trait characterized by sudden violence, explosive outbursts and hostile overreactions to stress.

In a study appearing today in the Journal of Neuroscience, researchers from the University of Southern California and Italy identify a critical neurological factor in aggression: a brain receptor that malfunctions in overly hostile mice. When the researchers shut down the brain receptor, which also exists in humans, the excess aggression completely disappeared.

The findings are a significant breakthrough in developing drug targets for pathological aggression, a component in many common psychological disorders including Alzheimer's disease, autism, bipolar disorder and schizophrenia.

"From a clinical and social point of view, reactive aggression is absolutely a major problem," said Marco Bortolato, lead author of the study and research assistant professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy. "We want to find the tools that might reduce impulsive violence."

A large body of independent research, including past work by Bortolato and senior author Jean Shih, USC University Professor and Boyd & Elsie Welin Professor in Pharmacology and Pharmaceutical Sciences at USC, has identified a specific genetic predisposition to pathological aggression: low levels of the enzyme monoamine oxidase A (MAO A). Both male humans and mice with congenital deficiency of the enzyme respond violently in response to stress.

"The same type of mutation that we study in mice is associated with criminal, very violent behavior in humans. But we really didn't understand why that it is," Bortolato said.

Bortolato and Shih worked backwards to replicate elements of human pathological aggression in mice, including not just low enzyme levels but also the interaction of genetics with early stressful events such as trauma and neglect during childhood.

"Low levels of MAO A are one basis of the predisposition to aggression in humans. The other is an encounter with maltreatment, and the combination of the two factors appears to be deadly: it results consistently in violence in adults," Bortolato said.

The researchers show that in excessively aggressive rodents that lack MAO A, high levels of electrical stimulus are required to activate a specific brain receptor in the pre-frontal cortex. Even when this brain receptor does work, it stays active only for a short period of time.

"The fact that blocking this receptor moderates aggression is why this discovery has so much potential. It may have important applications in therapy," Bortolato said. "Whatever the ways environment can persistently affect behavior — and even personality over the long term — behavior is ultimately supported by biological mechanisms."

Importantly, the aggression receptor, known as NMDA, is also thought to play a key role in helping us make sense of multiple, coinciding streams of sensory information, according to Bortolato.

The researchers are now studying the potential side effects of drugs that reduce the activity of this receptor.

"Aggressive behaviors have a profound socio-economic impact, yet current strategies to reduce these staggering behaviors are extremely unsatisfactory," Bortolato said. "Our challenge now is to understand what pharmacological tools and what therapeutic regimens should be administered to stabilize the deficits of this receptor. If we can manage that, this could truly be an important finding."

Sean Godar, a postdoctoral student in the department of molecular pharmacology and toxicology at the USC School of Pharmacy, was co-lead author of the study. Kevin Chen, a research associate professor at the USC School of Pharmacy, was a co-author on the study. The research was funded by the National Institute of Mental Health of the National Institutes of Health under grant R01MH39085, the National Institute of Child Health and Human Development of the National Institutes of Health under grant R21HD070611, the Boyd and Elsie Welin Professorship help by Shih, and a USC Zumberge Research Individual Grant to Bortolato.

Suzanne Wu | EurekAlert!
Further information:
http://www.usc.edu

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>