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Utah researchers discover link between certain brain cells and anxiety, OCD

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SALT LAKE CITY — Mental health is blamed for a lot of issues plaguing society these days, but scientists and biologists still know very little about what’s happening inside the brain that brings on problems in certain people.

A group of researchers at the University of Utah, however, may now have a clue.

They’ve identified a link between a group of specialized brain cells, called Hoxb8-lineage microglia, and obsessive compulsive disorder and anxiety in mice.

Similar to humans, female mice are more susceptible to the anxiety-related diseases, though symptoms were observed in male mice, too. The discovery could lead to the development of drugs better suited to treat and/or prevent anxiety and OCD.

“It opens up a new avenue for thinking about anxiety,” said Dimitri Tränkner, a lead author of the study and assistant biology professor at the U. “Since we have this model, we have a way to test new drugs to help these mice and hopefully at some point, this will help people.”

The findings suggest a link between biological sex hormones (estrogen and progesterone) and genetics, two major risk factors for anxiety-related disorders in humans, according to the study published this week in Cell Reports.

Until now, it was unknown whether this subset of microglia, which play a crucial role in brain development in the womb, had any other function at all. The new findings build upon previous mice studies conducted by Nobel laureate Mario Capecchi, also a lead author in the new research.

Capecchi had long suspected this subset of microglia was special in some way, but researchers didn’t pick up on certain behaviors related to anxiety, such as overgrooming, until this time around — it’s the first study to describe the role of microglia in OCD and anxiety in this way.

“We didn’t really know what to make of the fact that mice without Hoxb8 appear so normal, until we noticed that they groom significantly more and longer than what would be considered healthy,” said Capecchi, a distinguished professor of human genetics at the U.

“Scientists want to help these people to get their lives back.” — Dimitri Tränkner, a lead author of the study

To test whether sex hormones drove OCD and anxiety symptoms, Tränkner and his colleagues manipulated estrogen and progesterone levels in the mice. They found that at male-levels, the OCD and anxiety behaviors in female mice resembled the male response, and at female hormone levels, the OCD behaviors in male mice looked more like the female’s severe symptoms, and showed signs of anxiety.

“We have a good understanding of how anxiety is produced in people,” but cannot do experiments in people, Tränkner said. “Of all models, I have great faith that mice are one of the best models, as they are so similar to people.”

He said some of the mice had significant hair loss, were more easily “stressed out,” or lost their natural fight-or-flight response mechanisms without the protective presence of the microglia in their brains.

It shows that the two phenomena are related.

Researchers have long suspected that microglia have a role in anxiety and other neuropsychological disorders in humans because this type of cell can also release substances to harm neurons.

“It’s surprising to see that (the microglia) are not causing it, but they can protect from it,” Tränkner said, adding that researchers and biologists now have an explanation as to why anxiety-related diseases are more common in women.

“This news should give hope ... for many reasons,” he said.

Science has long tried to find solutions for people who deal with the life-altering mental illnesses, and Tränkner said this puts everyone that much closer to new drugs to treat them, particularly anxiety.

“Scientists want to help these people to get their lives back,” he said.