Summary: A new study reveals that the protein Reelin may hold the key to treating both “leaky gut” and major depressive disorder. Chronic stress lowers Reelin levels in the gut, weakening the intestinal barrier and allowing toxins to trigger inflammation that worsens depression.
Researchers found that a single injection of Reelin restored normal levels, strengthening gut integrity and potentially improving mood. The findings suggest a powerful new therapeutic approach that targets the gut–brain axis to heal both body and mind.
Key Facts:
- Dual-Action Protein: Reelin regulates both brain and gut health, restoring intestinal integrity and supporting mood balance.
- Stress Connection: Chronic stress reduces Reelin in the gut, leading to inflammation and worsening depression.
- Therapeutic Potential: A single injection of Reelin normalized gut levels and showed antidepressant-like effects in preclinical models.
Source: University of Victoria
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,” says Caruncho. “The gut-brain axis is becoming essential to understanding many psychiatric disorders, including depression.”
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.
Funding: 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).
Key Questions Answered:
A: Reelin is a glycoprotein found throughout the body that supports neuron function, regulates the gut barrier, and promotes tissue renewal.
A: Chronic stress can cause “leaky gut,” letting toxins enter the bloodstream and trigger inflammation that contributes to depressive symptoms.
A: By repairing gut integrity and improving brain chemistry simultaneously, Reelin could become a dual-target treatment for depression and gut disorders.
About this depression and microbiome research news
Author: Heather Walmsley
Source: University of Victoria
Contact: Heather Walmsley – University of Victoria
Image: The image is credited to Neuroscience News
Original Research: Open access.
“An Intravenous Injection of Reelin Rescues Endogenous Reelin Expression and Epithelial Cell Apoptosis in the Small Intestine Following Chronic Stress” by Ciara Halvorson et al. Chronic Stress
Abstract
An Intravenous Injection of Reelin Rescues Endogenous Reelin Expression and Epithelial Cell Apoptosis in the Small Intestine Following Chronic Stress
Chronic stress disrupts the integrity of the gut environment, including leaking of the intestinal epithelium.
Reelin, an extracellular matrix protein, is released from cells of the lamina propria and promotes epithelial cell proliferation and migration up the crypt-villus axis to facilitate renewal of the gut lining.
In the present study, we evaluated Reelin expression and apoptosis in the small intestine of Long Evan’s rats treated with recombinant Reelin (3 µg) or vehicle following 3 weeks of daily corticosterone (40 mg/kg/day) or vehicle injections.
We show that Reelin- and cleaved caspase-3- immunoreactive cells are diminished in the lamina propria or epithelial cells of the gut lining following chronic stress (∼ 50% and 55%, respectively), and that a single injection of 3 µg of Reelin delivered intravenously can reverse these parameters.
We also found Reelin cell counts in the small intestine did not correlate to counts in the hippocampus regardless of exposure to chronic stress or Reelin treatment.
Our results suggest that Reelin may serve a protective function over gut barrier integrity through the restoration of epithelial cell turnover, and that Reelin may have a role in reversing chronic stress-induced changes to the gut environment.
