The shared anger of mice and men: Scientific breakthrough linking humans to rodents could lead to new treatments for Alzheimer's and autism
By Rob Preece
It is one of life's great mysteries - how some people can fly off the handle and become aggressive and violent seemingly without warning.
But scientists now believe they know why some humans are more likely to show aggression than others, after they managed to block pathological rage in mice.
Researchers found that overly hostile mice and angry men share biological similarities which make them more susceptible to rage - a major breakthrough which could pave the way for new treatments for conditions including Alzheimer's disease and autism.
Breakthrough: Researchers found that overly hostile mice and angry men share biological similarities which make them more susceptible to rage
In a study published in the Journal of Neuroscience, researchers from the University of Southern California and Italy identified a brain receptor in mice, which malfunctions in overly hostile rodents.
When the scientists shut down the brain receptor, which also exists in humans, the excess aggression disappeared.
The findings are expected to help experts develop drug targets for pathological aggression, which is a component in Alzheimer's, autism, bipolar disorder and schizophrenia.
Marco Bortolato, the study's lead author and an assistant professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy, told Science Daily: 'From a clinical and social point of view, reactive aggression is absolutely a major problem.
'We want to find the tools that might reduce impulsive violence.'
Scientists had already found that both male humans and mice respond violently to stress if they have low levels of the enzyme monoamine oxidase A (MAO A).
Similarities: Scientists found that both male humans and mice respond violently to stress if they have low levels of the enzyme monoamine oxidase A
'The same type of mutation that we study in mice is associated with criminal, very violent behaviour in humans,' Bortolato said.
'But we really didn't understand why that is.'
Bortolato and his USC colleague Jean Shih worked backwards to replicate elements of human pathological aggression in mice.
This meant not only low enzyme levels but also the interaction of genetics with early stressful events, such as trauma and childhood neglect.
'Low levels of MAO A are one basis of the predisposition to aggression in humans,' Bortolato.
'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.'
The research found that, in excessively aggressive rodents lackomh MAO A, high levels of electrical stimulus are required to activate a specific receptor in the brain.
Even when this brain receptor does work, it stays active only for a short period of time.
Bortolato said: 'The fact that blocking this receptor moderates aggression is why this discovery has so much potential. It may have important applications in therapy.
'Whatever the ways environment can persistently affect behaviour - and even personality over the long term - behaviour is ultimately supported by biological mechanisms.'