Inflammatory protein levels linked to aggressive behaviour

Aggression is common in many neuropsychiatric diseases — such as dementia, autism spectrum disorder and schizophrenia — but can be difficult to treat because little is known about what causes it. Researchers have now revealed that variation in levels of interleukin 1β (IL-1β), a protein that mediates the inflammatory response, is associated with individual differences in aggressive behaviours in male mice; their results have been published in the journal Molecular Psychiatry.

In humans, levels of inflammatory proteins such as IL-1β in the blood correlate with aggressive traits. To better understand these findings, researchers at the University of Tsukuba and the Icahn School of Medicine at Mount Sinai decided to investigate IL-1β levels in the blood of male mice, which they classified as aggressive or non-aggressive based on their behaviours towards other male mice.

Unexpectedly, the researchers found no differences in blood IL-1β levels between the aggressive and non-aggressive mice, in contrast to what had been reported in humans. This intrigued the researchers, who wanted to know more.

“The dorsal raphe nucleus is a region of the brain that is important in aggressive behaviours,” said lead author Professor Aki Takahashi, from the University of Tsukuba and Mount Sinai. “We decided to investigate IL-1β levels in this brain region in mice, and to experiment using drugs and genetic methods to reduce the effects of IL-1β on its receptors, to see if there were any related changes in aggressive behaviours.”

The results were surprising: IL-1β was actually lower in the dorsal raphe nucleus of aggressive mice than in non-aggressive mice. In addition, in the experiments where IL-1β was less able to act on its receptors in this brain region, the mice were more aggressive.

The researchers then decided to look at the relationship between IL-1β and serotonin, a key neurotransmitter in the control of aggression. They found that, during aggressive encounters, serotonin neurons in the dorsal raphe nucleus were more active in aggressive mice than in non-aggressive mice. Moreover, when they experimentally lowered the expression of IL-1 receptors, serotonin neurons were also more active in this brain region.

“Our findings suggest that IL-1β in the dorsal raphe nucleus suppresses aggressive behaviour, possibly by acting on the serotonin system,” Prof Takahashi said.

The findings suggest that IL-1β and serotonin neurons might be potential drug targets for reducing aggression, which currently has few effective treatments. The results could therefore lay the foundations for research into treatment approaches for aggression in patients with neuropsychiatric diseases.

Image credit: ©stock.adobe.com/au/lassedesignen

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