Healthcare (Commonwealth Union) – Anxiety disorders continue to be a serious concern across the globe. Yet scientists still have much to uncover about how anxiety originates in the brain. New findings from the University of Utah have revealed two unexpected sets of brain cells in mice that function like “gas pedals” and “brakes” for anxious behaviour.
Surprisingly, the cells controlling anxiety aren’t neurons — the nerve cells that connect to form networks and transmit messages throughout the body, but a connection with immunology. Instead, the key players appear to be microglia, a type of immune cell in the brain. One microglial group seems to trigger anxiety-like reactions, while another group works to suppress them.
Donn Van Deren, PhD, a postdoctoral researcher at the University of Pennsylvania who conducted the work while at University of Utah Health pointed out that it represents a major shift in our understanding and it demonstrates that when the brain’s immune system is compromised or unhealthy, it can lead to very specific psychiatric conditions.
The study is appeared in the journal Molecular Psychiatry.
Previous studies had already shown the team that microglia—the brain’s resident immune cells—play a key role in managing anxiety. However, earlier work suggested that all microglia behaved similarly. When they disrupted the function of one specific subgroup, known as Hoxb8 microglia, the mice began showing anxious behavior. But surprisingly, when they blocked the activity of all microglia at once—both Hoxb8 and non-Hoxb8—the mice appeared normal.
This pattern hinted that the two microglial populations might have opposing roles: Hoxb8 microglia may help reduce anxiety, while non-Hoxb8 microglia may help increase it. To confirm this, the scientists needed to observe each group acting independently.
Their conclusions depended on an unusual approach—transplanting specific types of microglia into mice that naturally lack these cells.
The team discovered that non-Hoxb8 microglia function like an accelerator for anxiety. When mice missing all microglia received transplants of only non-Hoxb8 cells, they began over-grooming and avoided open areas—well-known indicators of heightened anxiety. With just these cells present, the “anxiety accelerator” was stuck on, with no “brake” to counterbalance it.
By contrast, Hoxb8 microglia behaved like an anxiety brake. Mice given only Hoxb8 microglia showed no signs of anxiety. And importantly, mice that received both types of microglia—the accelerator and the brake—also remained calm. Although non-Hoxb8 microglia seemed to push the animals toward anxiety, their influence was counteracted by the calming effect of the Hoxb8 cells, resulting in normal behavior.
“These two populations of microglia have opposite roles,” said Mario Capecchi, PhD, distinguished professor of human genetics at University of Utah Health, who is also the senior author for the study. “Together, they set just the right levels of anxiety in response to what is happening in the mouse’s environment.”
The team believes their findings could form the basis for significant progress in understanding—and eventually treating—anxiety disorders. Capecchi pointed out that we humans also possess two types of microglia that behave in much the same way. However, most current psychiatric medications target neurons rather than these immune-related brain cells.
By pinpointing how non-neuronal cells contribute to anxiety, scientists may be able to design treatments that act directly on microglia—either boosting the calming “brake” signals or reducing the anxiety-promoting “accelerator” signals.
Capecchi indicated that this insight could help restore the ability of people who struggle to regulate their anxiety to take back control.
Van Deren however indicates that we are a long distance from making this therapeutic and in the future, scientists may possibly target very specific immune cell populations within the brain and make corrections via pharmacological or immunotherapeutic approaches.
The findings of the study may add a whole new dimension in anxiety treatment.
