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SALT LAKE CITY — More than 33% of adults in Utah 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, which was published a few weeks ago in the scientific journal Molecular Psychiatryresearchers discovered through cell stimulation that a specific brain cell called microglia not only acts as “a garbage collector” – a cell that disposes of dying brain 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 pathologically grooming themselves .
To better understand the functions of microglia, scientists used optogenetics, a method that uses a laser to stimulate cells through a combination of genetic engineering and laser technology. The same scientists then proceeded to expose the microglia cells to their mice test subjects and recorded how they responded.
By using laser exposure to open light-sensitive channels and cause an influx of ions into microglia, turning the laser on and off allows them to turn anxiety on and off, according to Capecchi.
The results, says Nagarajan, are impressive.
When microglia are turned on in different parts of the brain, the mice will show behaviors associated with anxiety, such as grooming themselves, freezing or generally increased anxiety. When the laser was turned off, the behaviors stopped immediately.
“What this means for human health, or what it means for the future is that the discovery is not just limited to stimulating cells and seeing behavior. The discovery is that these microglia cells are plays an important role in controlling neural circuit function,” Nagarajan said.
“Some anxieties and fixations are actually useful. We use anxiety to motivate us and fixations to comfort us. It’s too much when the anxiety becomes chronic or the fixation becomes pathological. that it’s too bad.”
– Mario Capecchi, Nobel laureate and senior author of the study
By understanding how microglia can control neural activity, Nagarajan and Capecchi can look at how microglia control works and possibly manage anxiety.
Capecchi added how an imbalance between the two different types of microglia also contributes to anxiety. As long as both types remain balanced, he said, anxiety and pathological adjustment can be managed; it is only when they are unbalanced that the pathological behavior is dominant.
“Some anxiety and fixation is actually beneficial. We use anxiety to motivate us and fixation to comfort us,” says Capecchi. “It is the excess that when the anxiety becomes chronic or the fixation becomes pathological that it is too bad.”
To expand the experiment, scientists will need to look at the types of chemicals released by microglia and how they trigger neurological behaviors. By looking at the chemicals that cause microglia reactions, Nagarajan said, they can better identify the root causes of anxiety — and, from there, figure out a way to best treat the disorder.
“We can correct the differences by targeting specific receptors or specific chemicals that are released by microglia — to really get us closer to therapies,” Nagajaran said. “We are in a position to say that this effect will be more specific than all the other drugs currently used in the field or on the market, which to some extent, alleviate the symptoms, but it does not cure the pain.”
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 in the beginning stages, but it’s a new beginning because no one has thought about using this kind of strategy,” Capecchi said. “The work is just — it’s just unveiling, it’s just coming out. There are hundreds of questions we can ask now.”
