Chronic stress inhibits autophagy—the brain's recycling system—but restoring its functionality yields rapid antidepressant effects. Digest
In small doses, stress can sharpen focus and improve resilience, but chronic stress gradually erodes emotional stability, increasing the risk of major depressive disorder. A recent study found that autophagy—the brain’s recycling and housekeeping system—helps maintain emotional stability by removing old or damaged proteins.
Researchers explored how short-term and long-term stress influenced autophagy in mice and investigated whether antidepressant drugs could restore this process. Employing genetic techniques, the researchers selectively inhibited or enhanced autophagy in a region of the brain called the lateral habenula and then monitored how the animals reacted to stress.
You just missed this in your inbox
Every other week our Premium Members received this exact study plus Rhonda's practical commentary and 8+ other hand-picked papers.
They found that acute stress activated autophagy, while chronic stress inhibited it. When autophagy ceased functioning properly, stress-related behaviors increased. However, restoring autophagy—even briefly—produced rapid antidepressant-like effects. Drugs commonly used to treat depression also reactivated autophagy in this brain region. Additional experiments indicated that autophagy helps regulate brain cell activity by breaking down excess glutamate receptors, which are often overactive in depression.
These findings suggest that disrupted autophagy in the lateral habenula plays a central role in how chronic stress contributes to depression. Learn more about autophagy in this episode featuring Dr. Guido Kroemer.