Can Exercise-Related Brain Proteins Help Explain Depression?

What you need to know

• A protein called FNDC5/irisin, which increases in the body during exercise, is reduced in the brains of people with major depression
• This reduction may help explain why exercise can help improve mood and depression symptoms
• The findings suggest a potential new pathway for developing depression treatments

The Exercise-Depression Connection

We’ve long known that regular exercise can help improve mood and reduce depression symptoms. But the biological mechanisms behind this connection have remained somewhat mysterious. Recent research has uncovered an intriguing protein that may help explain this relationship.

What is FNDC5/Irisin?

FNDC5/irisin is what scientists call a “myokine” - a protein released by muscle tissue during exercise. When we exercise, levels of this protein increase both in our bloodstream and in certain areas of our brain, particularly regions involved in memory and emotion. Previous research has shown that FNDC5/irisin plays important roles in brain health, including promoting the formation of new brain cells and supporting learning and memory.

What the Research Found

In this groundbreaking study, researchers examined brain tissue from individuals who had major depressive disorder (MDD) and compared it to tissue from people without depression. They discovered that levels of FNDC5/irisin were significantly lower in the prefrontal cortex - a brain region crucial for mood regulation - of people with depression.

The researchers then conducted several experiments with mice to better understand how different types of stress affect FNDC5/irisin levels in the brain. Interestingly, different forms of stress led to varying changes in FNDC5/irisin levels, highlighting the complexity of how this protein responds to different types of psychological challenges.

The Antidepressant Connection

The study also explored whether common antidepressant medications affect FNDC5/irisin levels in the brain. Among several medications tested, only fluoxetine (commonly known as Prozac) increased FNDC5/irisin levels in the mouse brain’s frontal cortex. This finding suggests that some antidepressants might work in part by affecting this exercise-related protein.

What This Means for You

These findings have several practical implications:

• The research provides additional scientific support for why exercise can be beneficial for mental health
• It suggests that combining exercise with traditional depression treatments might be particularly effective
• The discovery could lead to new treatments that target this protein system
• The findings reinforce the importance of maintaining regular physical activity for brain health

Conclusions

• Regular exercise might help combat depression in part through its effects on FNDC5/irisin in the brain
• Low levels of this exercise-related protein in the brain may contribute to depression
• Future treatments for depression might focus on ways to increase or maintain healthy levels of this protein in the brain