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| An astrocye from the striatum Image Credit: Joselyn Soto |
Scientific Frontline: Extended "At a Glance" Summary: The Role of Astrocytes in OCD
The Core Concept: Astrocytes, star-shaped cells in the brain traditionally viewed merely as a support system for neurons, actively participate in behaviors associated with obsessive-compulsive disorder (OCD).
Key Distinction/Mechanism: While OCD was previously thought to be driven primarily by neuronal dysfunction, research demonstrates that astrocytes in the striatum also express SAPAP3, a specific protein linked to compulsive behaviors. Restoring this protein in both astrocytes and neurons reduces compulsions, though only neurons appear to regulate the anxiety component of the disorder.
Major Frameworks/Components:
- Astrocytes: Star-shaped helper cells that provide structural and metabolic support to neurons, now recognized as active participants in psychiatric conditions.
- The Striatum: A distinct brain region responsible for decision-making and motor control, which is highly implicated in OCD pathology.
- SAPAP3 Protein: A specific protein whose absence triggers repetitive, OCD-like behaviors (such as compulsive grooming in mice), and which operates distinctly in neurons (affecting compulsion and anxiety) and astrocytes (affecting compulsion only).
Branch of Science: Neuroscience, Neurobiology, and Psychiatry.
Future Application: These findings could lead to novel, targeted pharmacological treatments for OCD that modulate astrocyte function, providing an alternative for patients who do not respond to standard antidepressants, psychotherapy, or both.
Why It Matters: Because conventional therapies fail a significant portion of the estimated 2% to 3% of the US population diagnosed with OCD, identifying a previously unknown cellular mechanism offers a critical new pathway for developing effective interventions for debilitating psychiatric disorders.
A type of cell usually characterized as the brain’s support system appears to play an important role in obsessive-compulsive disorder-related behaviors, according to new UCLA Health research.
The new clue about the brain mechanisms behind OCD, a disorder that is incompletely understood, came as a surprise to researchers. They originally sought to study how neurons interact with star-shaped “helper” cells known as astrocytes, which are known to provide support and protection to neurons.
However, scientists are still trying to understand the apparent role these complex cells play in psychiatric and neurodegenerative diseases.
By studying the proteins expressed by neurons and astrocytes in mice, UCLA researchers found a protein associated with OCD and repetitive behaviors in neurons was also found in astrocytes. The discovery suggests therapeutic strategies targeting astrocytes and neurons may be useful for OCD and potentially other brain disorders.
“Our research has revealed a new cellular mechanism, which not only involves neurons – something we already knew – but also involves astrocytes, working together,” said corresponding author Baljit Khakh, a professor of physiology and neurobiology at the David Geffen School of Medicine at UCLA. “Now we could expand our research in this area to cover additional mechanisms and cells.”
OCD, a lifelong anxiety disorder characterized by repetitive thoughts and actions, affects an estimated 2-3% of the U.S. population in their lifetimes, though its prevalence may be higher due to underreporting and underdiagnosis. Psychotherapy, antidepressant medication, or both are typically prescribed for OCD, but available treatment is ineffective for a sizable share of patients.
A brain region known as the striatum, which is involved in decision-making and motor control, is thought to play a key role in OCD. That is exactly the area of the brain the UCLA researchers studied when they sought to examine the interactions between astrocytes and neurons.
Khakh is among the researchers in recent years who have extensively studied astrocytes, thanks to technological advances that have made it more feasible to study these complex cells. While previous research has compared gene expression between neurons and astrocytes, this new study advanced our understanding of the interplay between the two cell types by analyzing protein expression.
“We really have to look at the proteins because they are very complex and diverse,” said co-author Joselyn Soto, a neuroscience PhD student at UCLA’s medical school. “Depending on which cell expresses which proteins, we can predict the functions of that cell.”
The researchers used multiple approaches to isolate and visualize proteins across neurons and astrocytes within the striatum. When they compared proteins found in neurons and astrocytes, they unexpectedly discovered both contained a protein associated with OCD known as SAPAP3.
The researchers tested their findings by inserting the SAPAP3 protein back into neurons and astrocytes of mice that had been genetically modified to lack the gene that makes the protein. They found that the two types of cells interacted in different ways when they measured the protein’s effects on compulsion and anxiety, two of the typical hallmarks of OCD.
The mice no longer compulsively groomed themselves after the SAPAP3 protein was delivered back to astrocytes and neurons, suggesting that both types of cells could be valid targets for treatments aimed at curbing compulsion. However, only neurons with the SAPAP3 protein were associated with reduced anxiety in the mice, suggesting that astrocytes would not be a good target for anxiety treatments in OCD.
Soto said future research would delve deeper into how the interactions between these cells affect behavior.
“These are both major cell types – one doesn’t work without the other,” Soto said. “We really wanted to understand how these multicellular interactions within this brain region give rise to these complex behaviors, including compulsion and anxiety.”
Adding that there needs to be more work to even understand how astrocytes are formed and maintained, Khakh said this new study’s unexpected findings demonstrated the value of pursuing basic biology questions to help form new ideas about the basis of diseases.
“This started from a basic question: What proteins make up this complex cell?” he said. “At the outset, we couldn’t have predicted its potential relevance to OCD.”
Reference material: What Is: Obsessive-Compulsive Disorder
Published in journal: Nature
Title: Astrocyte–neuron subproteomes and obsessive–compulsive disorder mechanisms
Authors: Joselyn S. Soto, Yasaman Jami-Alahmadi, Jakelyn Chacon, Stefanie L. Moye, Blanca Diaz-Castro, James A. Wohlschlegel & Baljit S. Khakh
Source/Credit: University of California Los Angeles, Health
Edited by: Scientific Frontline
Reference Number: ns041223_03
