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SALT LAKE CITY — Over 33% of adults in Utah have reported having symptoms of anxiety and/or depression — a figure that has only climbed in recent years. But a study conducted by University of Utah Health scientists may be one of the first steps toward understanding the root causes of anxiety and anxiety-related conditions, including obsessive-compulsive disorder.
In the study, published a few weeks ago in the scientific journal Molecular Psychiatry, researchers discovered through cell stimulation that a specific brain cell called microglia doesn't just act as "a trash collector" — a cell that disposes of the brain's dying neurons — but it can also control anxiety-related behaviors.
Naveen Nagarajan, a geneticist, neuroscientist and lead author of the study, and Nobel laureate Mario Capecchi first discovered that microglia contained a gene mutation called Hoxb8, which caused mice to exhibit anxiety-related and obsessive-compulsive behaviors, such as overgrooming themselves pathologically.
To further understand the microglia's functions, the scientists employed optogenetics, a method that uses a laser to stimulate cells through a combined feat of genetic engineering and laser technology. Both scientists then proceeded to expose microglia cells in their mice test subjects and record how they reacted.
By using laser exposure to open light-sensitive channels and cause an influx of ions into the microglia, switching the laser on and off allowed them to switch on and off the anxiety, according to Capecchi.
The results, Nagarajan said, were astonishing.
When lighting up the microglia in different areas in the brain, the mice would demonstrate anxiety-related behaviors, such as grooming themselves, freezing or generally increased anxiety. When switching off the laser, the behaviors immediately stopped.
"What it means for human health, or what it means for the future is that the discovery is just not restricted to stimulating the cells and seeing the behavior. The discovery is that these microglia cells make an essential role in controlling neural circuit function," Nagarajan said.
"Some anxiety and grooming is actually beneficial. We use anxiety to motivate us and grooming to comfort us. It's simply that too much when anxiety becomes chronic or grooming becomes pathological that it is too bad."
– Mario Capecchi, Nobel laureate and senior author of study
By understanding how the microglia could control neural activity, Nagarajan and Capecchi could then look into how controlling the microglia functions and potentially manage anxiety.
Capecchi added how the imbalance between two different types of microglia also contributes to anxiety. As both types remain balanced, he said, the anxiety and pathological grooming would be manageable; it's only when they're imbalanced that the pathological behavior dominates.
"Some anxiety and grooming is actually beneficial. We use anxiety to motivate us and grooming to comfort us," Capecchi said. "It's simply that too much when anxiety becomes chronic or grooming becomes pathological that it is too bad."
To further the experiment, the scientists will need to look into the types of chemicals the microglia release and how it triggers neurological behaviors. By looking into the chemical causes of the microglia reactions, Nagarajan said, they can better determine the root causes of anxiety — and, from there, figure out a way to best treat the disorder.
"We can correct those differences by targeting those particular receptors or those particular chemicals that are being released by microglia — so that will actually bring us close to therapies," Nagajaran said. "We will be in a position to say that this effect will be more specific than all the other drugs that are currently being used in the field or in the market, which to some extent, alleviate the symptoms, but it never cures the disease."
But the process of creating a drug and discovering therapies is still a long process that will take years to complete, according to Capecchi.
"We're at the beginning of the stages, but it's a brand new beginning because nobody thought about using this kind of approach," Capecchi said. "The work is just — it's just unveiling, it's just coming out. There are hundreds of questions we can ask now."
