The Immune System Is One Way That Stress Affects The Brain

Immune system alterations are linked to a number of stress-related mental diseases, including depression; nevertheless, the fundamental processes by which these alterations impact the brain remain mostly unclear. The University of Zurich, the University Hospital of Psychiatry Zurich (PUK), and the Icahn School of Medicine at Mount Sinai are leading an international research team that has recently discovered one such mechanism.

According to a report published in the journal Nature, the researchers demonstrated via animal models that stress causes a rise in the migration of white blood cells known as monocytes into the brain’s vascular system, especially into the areas of the reward center. The extracellular matrix, a net-like framework that envelops brain neurons, is reorganized and regulated by matrix metalloproteinase-8, which is produced by these monocytes.

“We were able to show that stress increases the amount of the matrix metalloproteinase-8 (MMP-8), an enzyme in the blood of mice,” stated Flurin Cathomas, the lead author, who is presently employed at the Icahn School of Medicine at Mount Sinai. From the blood, MMP-8 enters the brain and changes how some neurons operate. This causes behavioral abnormalities in the afflicted mice, who withdraw and shun social interaction.

“If MMP-8 penetrates the brain tissue from the blood, it changes the matrix structure and thus disrupts the functioning of the neurons,” Cathomas said. “Mice who are affected by this process display changes in behaviour that are similar to those seen in humans with depression.”

The researchers took the MMP-8 gene out of some of the mice to demonstrate that MMP-8 was, in fact, the cause of the behavioural abnormalities. These mice did not exhibit stress-related negative behavioral alterations in contrast to the control group.

“Blood analyses of patients with depression indicate that the findings from the mouse models are also relevant for humans: both the monocytes and MMP-8 were increased in the blood of people with depression in comparison to healthy participants,” Cathomas said.

Cathomas says that the results are novel in two ways.

“Firstly, they indicate a new ‘body–mind mechanism’, which might be relevant not only for stress-related mental illness, but also for other diseases that affect both the immune and nervous systems,” he said. Second, finding the particular MMP-8 protein may be the first step in creating novel depression therapies.

Cathomas stated that the work “demonstrates the importance of the interaction between the immune system and the brain in the development of psychiatric disorders,” even though many more studies are required before the findings can be applied in therapeutic practice. Today, psychiatric treatment already incorporates these concepts.

The research group is currently organizing clinical trials to find out how much stimulation of specific brain regions can affect the immune system. Additionally, they will examine whether any alterations in the immune system cells of individuals with depression affect how they behave.