Newly Discovered Brain Mechanism Reveals Link Between Microglia and Anxiety/OCD
Scientists from the University of Utah Health have conducted a study shedding light on the significant role of microglia, a lesser-known brain cell type, in the regulation of anxiety-related behaviors. This groundbreaking research challenges the conventional belief that behavior is solely controlled by neurons, the dominant cell type in the brain.
The study conducted by University of Utah Health scientists unveils the crucial role played by microglia, a minor brain cell type, in the modulation of anxiety and obsessive-compulsive spectrum disorder (OCSD) behaviors. By selectively stimulating specific populations of microglia, researchers were able to activate or inhibit these behaviors in mice. This discovery defies the notion that neurons are the sole regulators of behavior and offers new prospects for the development of anxiety treatment therapies.
Anxiety levels have soared due to the pandemic and its aftermath, yet the underlying causes of anxiety-related conditions, including OCSD, remain elusive. In a recent study, scientists from the University of Utah Health investigated the significance of microglia, a minor brain cell type, in controlling anxiety-related behaviors in laboratory mice. Traditionally, neurons have been considered the primary controllers of behavior.
The research team demonstrated that specific populations of microglia, akin to buttons on a game controller, can trigger anxiety and OCSD behaviors, while others can suppress them. Additionally, microglia interact with neurons to elicit these behaviors. The findings, published in the journal Molecular Psychiatry, open up new possibilities for targeted therapies in the future.
“The presence of a certain level of anxiety is beneficial,” says Nobel Laureate Mario Capecchi, Ph.D., a distinguished professor of human genetics at the Spencer Fox Eccles School of Medicine at the University of Utah and senior author of the study. “Anxiety serves as a motivation, propelling us forward and giving us that extra push that says, ‘I can do it.’ However, excessive anxiety overwhelms us, leading to mental paralysis, increased heart rate, sweating, and mental confusion.”
“This research is truly unique and challenges the established belief regarding the role of microglia function in the brain.”
The newly discovered mechanisms are crucial for maintaining behaviors within the healthy range under normal circumstances. However, under pathological conditions, these mechanisms can contribute to debilitating behaviors, explains Capecchi.
“This research is truly unique and challenges the established belief regarding the role of microglia function in the brain,” says Naveen Nagajaran, Ph.D, a geneticist and neuroscientist at the University of Utah Health and the lead author of the study.
Manipulating Microglia
Mice exhibiting OCSD-like behaviors display excessive self-grooming, leading to the loss of fur and the development of skin lesions. Previously, Capecchi’s team discovered that a gene mutation called Hoxb8 caused mice to exhibit chronic anxiety symptoms and excessive grooming. Surprisingly, they identified microglia, a type of immune cell, as the source of these behaviors. Microglia, which constitute only 10% of the brain’s cells, were traditionally known as “trash collectors” responsible for removing dying neurons, the most common type of brain cell, and abnormal proteins. Their findings were also among the first to demonstrate that Hoxb8 microglia played a significant role in behavior regulation through communication with specific neuronal circuits.
Distinguished Professor Mario Capecchi, Ph.D., and Naveen Nagajaran, Ph.D., University of Utah. Credit: Charlie Ehlert, University of Utah Health
However, the mechanisms through which microglia accomplish these tasks remained a mystery. To unravel more about this phenomenon, Nagajaran employed optogenetics, a technique that combines genetic engineering with laser light. Like controlling a video game, he used the laser to selectively stimulate specific populations of microglia in the brain.
To their astonishment, the researchers were able to induce anxiety-related behaviors with a simple flick of the switch. When they stimulated a specific subpopulation of microglia, known as Hoxb8 microglia, the mice became more anxious. Stimulating Hoxb8 microglia in other brain regions caused the mice to groom excessively. Targeting Hoxb8 microglia in yet another location had multiple effects: increased anxiety, excessive grooming, and freezing, indicating fear. When the laser was turned off, the behaviors ceased.
“That was a major surprise for us,” says Nagarajan. “It was conventionally believed that only neurons could generate behaviors. These findings shed light on a second mechanism through which the brain generates behaviors involving microglia.” Furthermore, stimulating microglia with the laser led to increased neuronal activity in the adjacent cells, indicating that these two cell types communicate with each other to drive distinct behaviors.
Distinguished Professor Mario Capecchi, Ph.D., and Naveen Nagajaran, Ph.D., University of Utah. Credit: Charlie Ehlert, University of Utah Health
Further experiments unveiled an additional layer of control by a population of microglia that do not express Hoxb8. Simultaneously stimulating these “non-Hoxb8” microglia and Hoxb8 microglia prevented the onset of anxiety and OCSD-like behaviors. These results suggest that the two populations of microglia act as a brake and an accelerator, balancing each other out under normal conditions but leading to a diseased state when the signals are imbalanced.
The research highlights the significance of microglia location and type as key factors in fine-tuning anxiety and OCSD behaviors. Microglia communicate with specific neurons and neural circuits, ultimately regulating behavior, explains Capecchi. “We aim to delve deeper into the bidirectional communication between neurons and microglia,” he adds. “We want to understand the underlying mechanisms responsible for this interaction.” By defining these interactions in mice, potential therapeutic targets for controlling excessive anxiety in patients could be identified.
Reference: “Optogenetic stimulation of mouse Hoxb8 in specific regions of the brain induces anxiety, grooming, or both” by Naveen Nagarajan and Mario R. Capecchi, 10 April 2023, Molecular Psychiatry.
DOI: 10.1038/s41380-023-02019-w
Table of Contents
Frequently Asked Questions (FAQs) about microglia and anxiety
What is the role of microglia in anxiety and OCD?
Microglia, a minor cell type in the brain, have been found to play a significant role in regulating anxiety and obsessive-compulsive spectrum disorder (OCD) behaviors. Certain populations of microglia can trigger these behaviors, while others can inhibit them.
How does this research challenge the belief about behavior control in the brain?
This research challenges the conventional belief that behavior is solely controlled by neurons, the dominant cell type in the brain. It reveals that microglia, previously considered as “trash collectors,” have the ability to influence and regulate behaviors related to anxiety and OCD.
What are the potential implications of this research?
The findings open up new possibilities for targeted therapies for anxiety treatment. Understanding the interactions between microglia and neurons could lead to the identification of therapeutic targets to control excessive anxiety in patients.
How were the effects of microglia on behavior studied?
The researchers used optogenetics, a technique combining genetic engineering and laser light, to selectively stimulate specific populations of microglia in the brain. By stimulating or inhibiting these microglia, they were able to induce or suppress anxiety-related behaviors in mice.
What is the significance of Hoxb8 microglia in behavior regulation?
Hoxb8 microglia were found to be crucial in controlling anxiety and OCD behaviors. Stimulating these specific microglia populations led to the manifestation of these behaviors, while inhibiting them had the opposite effect. The communication between Hoxb8 microglia and neurons plays a vital role in driving distinct behaviors.
How can this research contribute to the development of anxiety treatments?
By unraveling the mechanisms of microglia’s role in anxiety regulation, this research provides valuable insights that could lead to the development of targeted therapies. Understanding the interactions between microglia and neurons may help identify specific therapeutic targets for controlling excessive anxiety in individuals.
More about microglia and anxiety
- University of Utah Health: Link to University of Utah Health website
- Molecular Psychiatry: Link to the study published in Molecular Psychiatry
- Optogenetics: Link to more information on optogenetics
- Hoxb8: Link to more information on the Hoxb8 gene
- Neurons: Link to more information on neurons
- Anxiety Treatment Therapies: Link to resources on anxiety treatment therapies
6 comments
Microglia, small cells with big impact. They balance our behaviors like a delicate ecosystem. Understanding their role in anxiety brings us closer to finding harmony within ourselves.
This research challenges the status quo in brain science. Forget what we thought we knew about neurons! Microglia have stepped into the spotlight, revealing their role in anxiety. The past is history, the future is microglia!
Wow, this study shows that microglia, those little brain cells, can affect anxiety and OCD! That’s mind-blowing. Neurons aren’t the only players here!
This research is amazing! Who would’ve thought that microglia, the trash collectors of the brain, could control our behaviors? Such a cool discovery!
Microglia rule! They’re like the button pushers in a game, turning on anxiety or compulsive behaviors. Neurons better watch out, there’s a new player in town!
Microglia and neurons, a dynamic duo! They communicate to drive different behaviors. Who knew those tiny brain cells had such an important role? Science is fascinating!