Reelin protein may help heal both "leaky gut" and severe depression

What if a protein could be injected to help heal both "leaky gut" and severe depression? New research from the University of Victoria (UVic), published in Chronic Stress, shows that a glycoprotein called Reelin may one day be able to do just that. 

In a healthy body, the gastrointestinal system - which includes stomach, colon, and intestines, and is often referred to as the "gut" - controls which nutrients enter the bloodstream. When a person experiences chronic stress, or a stress-related condition such as major depressive disorder (MDD), the gut barrier can become more permeable.

This "leaky gut" can then allow harmful bacteria and toxins to enter circulation, which can lead to an immune system reaction and inflammation. This can further exacerbate symptoms of depression. Treatments that restore the integrity of the gut barrier may therefore be helpful in preventing MDD. 

Reelin-based therapeutics could potentially offer such treatment, according to Hector Caruncho, professor of medical sciences at UVic and corresponding author on the study. Reelin is a protein that is found throughout the human body, including in the brain, blood, liver and intestines. 

This study aimed to understand the role of Reelin in the gut, especially under conditions of chronic stress. The gut-brain axis is becoming essential to understanding many psychiatric disorders, including depression." 

Hector Caruncho, professor of medical sciences at UVic 

The study found that chronic stress decreased Reelin in the intestines of preclinical models, and that a single injection of 3 µg of Reelin normalized levels. 

Previous studies have shown that individuals diagnosed with major depressive disorder have less Reelin in their brains, as do rodents exposed to chronic stress, and that a single intravenous injection of 3 µg of Reelin can produce antidepressant-like effects in these rodents. They have also shown Reelin to be necessary for proper gut lining renewal.

"Taken together, these results may have important implications for the management of major depressive disorder," says Ciara Halvorson, neuroscience PhD student at UVic, and first author on the paper. "This is especially true for people who live with both depression and gastrointestinal conditions. 

"Under healthy conditions, the gut lining is renewed every four to five days. This is important as the cells in the gut lining are constantly exposed to damaging factors in the gut. 

"If Reelin protects against leaky gut by supporting the renewal of the gut lining, Reelin may thereby protect against the worsening of depression symptoms triggered by inflammatory immune responses to leaked gut material." 

While more research is needed before Reelin will be available in the clinic, these findings position Reelin as a promising new treatment for depression that targets processes in both the brain and the gut.

This study was supported by funding from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC).