How Do Brain Cells Work Together in OCD? New Insights from Protein Studies

What you need to know

• Scientists discovered that both nerve cells and support cells called astrocytes play important roles in obsessive-compulsive disorder (OCD)
• A protein called SAPAP3, which is linked to human OCD, works differently in these two cell types to influence OCD-like behaviors
• Understanding how different brain cells contribute to OCD could lead to better treatments targeting multiple cell types

Background on OCD and Brain Cells

Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. It causes intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that can significantly impact daily life. While we know OCD involves problems in brain circuits, especially in a region called the striatum, the detailed molecular mechanisms aren’t well understood.

The brain contains two major cell types that work together: neurons (nerve cells that transmit signals) and astrocytes (star-shaped support cells that maintain brain health). While most research has focused on neurons, mounting evidence suggests astrocytes also play important roles in brain disorders.

A New Way to Study Brain Cell Proteins

The research team developed an innovative method to study proteins in both neurons and astrocytes while preserving their natural structure and connections. This was important because traditional methods of isolating brain cells can damage them and alter their protein content.

Using specially engineered viruses, they delivered a protein-tagging molecule to either neurons or astrocytes in mouse brains. This allowed them to identify which proteins were present in each cell type and where they were located within the cells.

Key Findings About Cell-Specific Proteins

The study revealed that neurons and astrocytes have both shared and unique protein machinery:

• Neurons contained many proteins involved in electrical signaling and communication between cells
• Astrocytes had proteins specialized for maintaining brain chemistry and structure
• Both cell types shared proteins for basic cellular functions
• They found that protein levels didn’t always match gene activity levels, highlighting the importance of studying proteins directly

The SAPAP3 Connection to OCD

A key discovery involved a protein called SAPAP3, which has been linked to OCD in humans through genetic studies. Previous research focused mainly on SAPAP3’s role in neurons, but this study found it was equally abundant in astrocytes.

The researchers found that SAPAP3 had different jobs in each cell type:

• In neurons, it helped organize proteins at synapses (connection points between neurons)
• In astrocytes, it helped maintain cell structure and regulate how the cells take up chemicals from their environment

Testing SAPAP3’s Role in OCD-Like Behaviors

The team used mice lacking SAPAP3 protein, which show OCD-like behaviors such as excessive grooming and anxiety. They then selectively restored SAPAP3 in either neurons or astrocytes to see how this affected behavior.

Their findings showed that both cell types were important:

• Restoring SAPAP3 in either cell type reduced excessive grooming
• Only restoring SAPAP3 in neurons reduced anxiety-like behaviors
• Both approaches normalized overactive brain circuits in the striatum

A New View of Brain Disorders

This research challenges the traditional neuron-centered view of brain disorders. It shows that:

1. Multiple cell types can contribute to psychiatric conditions
2. The same protein can have different but important roles in different cell types
3. Treatment strategies might need to target both neurons and astrocytes

The findings align with human studies showing that many genes linked to OCD are active in both neurons and astrocytes. This suggests that considering multiple cell types could be important for understanding and treating not just OCD, but potentially other brain disorders as well.

Conclusions

• Both neurons and astrocytes contribute to OCD-like behaviors through distinct molecular mechanisms
• The protein SAPAP3 serves different but important functions in each cell type
• Future treatments for OCD might be more effective if they target both cell types
• This research provides a new framework for understanding how different brain cells work together in health and disease