When anxiety takes hold, it’s a full-body experience. It’s hard to imagine that these all-encompassing symptoms could emanate from a few specific cells,but new research points to just such a neural home for anxiety in the brain.
Using a specific class of cells as a target, researchers hope that they’ll be able to develop more precise and effective treatments for anxiety. A new treatment that could prevent anxiety symptoms may be lurking in a small population of microglia is described in a paper published this week in Cell Reports. In a series of mouse experiments, scientists at the University of Utah noted that a “lineage” of cells called Hoxb8 microglia had specific effects on anxiety. In mice with dysfunctional Hoxb8 microglia cells, they nervously over-groomed and displayed symptoms similar to human anxiety and obsessive-compulsive disorder, but when these cells were functioning normally, the symptoms abated. Dimitri Traenkner, Ph.D., assistant professor of biology at the University of Utah, tells Inverse the finding offers a biological answer for why people with acute anxiety feel the way they do. The identification of these cells is a big step forward for developing new anxiety treatments.“For people suffering from anxiety, this news should give hope. Maybe simply because it might not be your fault if you are anxious. There is an underlying disease mechanism,” Traenkner says. In the past year, the National Institute of Mental Health estimated that about 19.1 per cent of adults in the United States suffered from an anxiety disorder which means that their anxiety was so acute that it affected their jobs, schoolwork, and relationships.“An underlying disease mechanism”.
Using a specific class of cells as a target, researchers hope that they’ll be able to develop more precise and effective treatments for anxiety. A new treatment that could prevent anxiety symptoms may be lurking in a small population of microglia is described in a paper published this week in Cell Reports. In a series of mouse experiments, scientists at the University of Utah noted that a “lineage” of cells called Hoxb8 microglia had specific effects on anxiety. In mice with dysfunctional Hoxb8 microglia cells, they nervously over-groomed and displayed symptoms similar to human anxiety and obsessive-compulsive disorder, but when these cells were functioning normally, the symptoms abated. Dimitri Traenkner, Ph.D., assistant professor of biology at the University of Utah, tells Inverse the finding offers a biological answer for why people with acute anxiety feel the way they do. The identification of these cells is a big step forward for developing new anxiety treatments.“For people suffering from anxiety, this news should give hope. Maybe simply because it might not be your fault if you are anxious. There is an underlying disease mechanism,” Traenkner says. In the past year, the National Institute of Mental Health estimated that about 19.1 per cent of adults in the United States suffered from an anxiety disorder which means that their anxiety was so acute that it affected their jobs, schoolwork, and relationships.“An underlying disease mechanism”.
Before Traenkner’s team revealed the connection between microglia and anxiety symptoms in mice, scientists knew these cells had both a good side and a bad side. Microglia act as maintenance cells in the brain that seek out pathogens and destroy them. However, the activation of microglia has also been traced to neurodegenerative diseases, like Alzheimer’s, suggesting that we don’t fully understand how their benefits compared to their potential for harm. That strange dichotomy made it even more surprising when this team found that microglia may have a protective effect on anxiety symptoms. In the paper, they explain that these cells have “the ability to suppress obsessive-compulsive and anxiety symptoms.”The researchers also seem to have solved another piece of the microglia puzzle: the Only microglia that develop a specific way seems to have this protective effect of suppressing anxiety symptoms. All microglia start out as a common precursor cell similar to the way that all living creatures descended from a common ancestor. The cells then follow certain pathways of development that make them distinct from each other. These specific microglia develop according to the whims of the Hoxb8 gene, which is why they’re named Hoxb8 microglia.
To test whether these cells affected anxiety symptoms, the team messed with that development pathway, making it impossible for those cells to follow the garden path from a common precursor to fully differentiated microglia. Getting off track in this way led to higher rates of anxiety and OCD.“The main positive aspect is that our study, and many recent studies done in other labs, show that we are getting closer to defining the cells and molecules producing or preventing anxiety,” says Traenkner. Supporting this claim, they noticed another way that human anxiety is mirrored in these cells deep in mouse brains: in how anxiety symptoms are linked to male and female hormones. Hormones and symptom severity.People of both sexes struggle with anxiety, but females tend to struggle more with it, statistically speaking. In the past year, the NIH noted that 23.4 per cent of women were diagnosed with an anxiety order compared to 14.3 per cent of men. This team suggests that if the microglia play a role in the development of symptoms in the first place, hormones appear to control how severe those symptoms are. In this study, female mice who had abnormal Hoxb8 microglia showed more severe symptoms than their male counterparts. Both male and female mice started showing coat loss due to over-grooming when they were three weeks old (a sign of anxiety), but the females started losing their hair rapidly when they were between six and eight weeks old, which is when they started to reach sexual maturity and were producing more estrogen and progesterone. To test whether those primary female sex hormones could increase anxiety symptoms, they actually reduced the mice’s production of those hormones. In response, over-grooming plummeted to levels similar to those seen in male mice.
Their experiment suggests that it’s the high levels of estrogen and progesterone that could ratchet up the volume of anxiety symptoms in females, particularly around the onset of puberty. Though this was only seen in their mouse models, we do see higher levels of anxiety in adolescent girls compared to boys. Thirty-eight per cent of adolescent girls had anxiety disorders in the past year, compared to 26.1 per cent of adolescent boys.Taken together, Traenkner is most excited about the potential that his team’s early research has for explaining anxiety, a condition that feels overwhelming and hard to explain for both patients and physicians. This model, he says is just at the beginning, but he has plans to keep probing at it.“At this point, I have only a vision,” he says. “But experiments will tell.”