Could a single injection of a glycoprotein mend both a “leaky gut” and severe depression? A study from the University of Victoria, published in Chronic Stress, suggests that the protein reelin might be the key.
Chronic StressThe gut—made up of the stomach, colon and intestines—regulates which nutrients pass into the bloodstream. Under chronic stress or stress‑related illnesses such as major depressive disorder (MDD), the gut lining can become more permeable.
When the barrier is compromised, harmful bacteria and toxins can enter the body, provoking immune responses and inflammation that can worsen depressive symptoms. Therapies that restore gut integrity might therefore help prevent or reduce MDD.
Reelin, a protein distributed throughout the body—including brain, blood, liver and gut—could serve this purpose, according to Hector Caruncho, a UVic medical sciences professor and lead author of the study.
"Our goal was to explore how reelin functions in the gut during chronic stress," Caruncho explains. "The gut‑brain axis is increasingly recognized as central to many psychiatric conditions, depression included."
The research demonstrated that chronic stress lowered reelin levels in the intestines of animal models, and that a single 3 µg injection brought the levels back to normal.
Other studies have found reduced brain reelin in people with MDD and in stressed rodents, and that a 3 µg injection can produce antidepressant‑like effects. Reelin is also essential for maintaining and renewing the gut lining.
"These findings could significantly influence how we treat major depressive disorder," says Ciara Halvorson, UVic neuroscience Ph.D. student and the paper’s first author. "They are particularly relevant for patients dealing with both depression and gastrointestinal issues."
Under healthy conditions the gut lining renews every four to five days, a process that keeps cells protected against constant gut irritants. If reelin aids gut renewal and prevents leakage, it may also reduce the inflammation that intensifies depression symptoms.
Although further research is necessary before reelin becomes an approved clinical therapy, the study positions it as a promising treatment that targets both the brain and gut.