Circulating myeloid-derived MMP8 in stress susceptibility and depression. (https://pubmed.ncbi.nlm.nih.gov/38326622/)

These scientists wanted to understand how stress affects our bodies and brains. They studied a protein called matrix metalloproteinase 8 (or MMP8 for short) that is found in our blood. They found that people with a condition called major depressive disorder (or MDD) had higher levels of MMP8 in their blood. They also found that mice who were exposed to chronic social defeat stress (which means they were constantly feeling stressed) had more MMP8 in their blood too.

The scientists then looked at the brains of these stressed mice and found that the increased levels of MMP8 caused changes in a specific part of the brain called the nucleus accumbens (or NAc for short). These changes affected how the brain cells communicate with each other and also how the mice behaved socially.

To understand how stress affects the immune system, the scientists looked at different types of immune cells in the blood and the brain of the stressed mice. They found that a specific type of immune cell called monocytes was strongly affected by stress. These monocytes had higher levels of MMP8 in both the blood and the brain of the stressed mice.

The scientists then discovered that the MMP8 from the blood could enter the brain and affect the structure of the brain cells. This caused changes in how the brain worked and how the mice behaved socially. When the scientists removed MMP8 from the stressed mice, they found that the mice no longer showed social avoidance behavior and their brain cells went back to normal.

Based on all these findings, the scientists believe that stress can affect our immune system and our brain. They think that by targeting the MMP8 protein, they may be able to develop new treatments for stress-related disorders like depression.

Cathomas F., Lin HY., Chan KL., Li L., Parise LF., Alvarez J., Durand-de Cuttoli R., Aubry AV., Muhareb S., Desland F., Shimo Y., Ramakrishnan A., Estill M., Ferrer-Perez C., Parise EM., Wilk CM., Kaster MP., Wang J., Sowa A., Janssen WG., Costi S., Rahman A., Fernandez N., Campbell M., Swirski FK., Nestler EJ., Shen L., Merad M., Murrough JW., Russo SJ. Circulating myeloid-derived MMP8 in stress susceptibility and depression. Nature. 2024 Feb 7. doi: 10.1038/s41586-023-07015-2.