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!
When predictions of theoretical chemists become reality
22.05.2020 | Technische Universität Dresden
From artificial meat to fine-tuning photosynthesis: Food System Innovation – and how to get there
20.05.2020 | Potsdam-Institut für Klimafolgenforschung
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.
Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...
Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.
A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...
By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.
Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...
Study co-led by Berkeley Lab reveals how wavelike plasmons could power up a new class of sensing and photochemical technologies at the nanoscale
Wavelike, collective oscillations of electrons known as "plasmons" are very important for determining the optical and electronic properties of metals.
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
25.05.2020 | Medical Engineering
25.05.2020 | Information Technology
25.05.2020 | Information Technology