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!
New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego
Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
16.01.2018 | Materials Sciences
16.01.2018 | Materials Sciences
16.01.2018 | Power and Electrical Engineering