Special immune cells in the brain, microglia, play a key role in the processes that make you feel uncomfortable and depressed due to inflammation. This is the result of a study conducted on mice by researchers at Linköping University in Sweden. The results have been published in the scientific journal immunity, And indicates that microglia contribute to negative moods that occur during many neurological diseases and possibly depression.
David Engbloom’s research group at Linköping University has spent many years researching why inflammation in the body, such as the common cold or the flu, makes us feel weak and hopeless, and why we feel the urge to retire in our shell. Immune system activity affects nerve cells in some way. However, the normal cells of the immune system are unable to enter the brain: they are sensitive and must be protected. Instead, the brain has its own immune cells: glial cells.
Previous research has shown that microglia is active in several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and stroke. People with these conditions often fall into negative moods. Other previous research has indicated that inflammatory processes also play a role in the development of depression. This led the researchers behind the new study to study whether glial cells are involved in mood regulation during inflammation.
The study showed that animals feel sick and uncomfortable when we stimulate microglia. We show that the two signaling molecules, interleukin-6 and prostaglandin E2, are particularly important in these processes. It is not surprising that these signals are central, but we were a little surprised that it is the microglia that release these particles, ”says David Engblom, a professor in the Department of Biomedical and Clinical Sciences (BKV) at Linköping University.
During inflammation, several processes begin in several types of cells. Therefore, one of the challenges in determining the role a specific type of cell plays in the body is isolating its effects. In this study, the scientists used a technique known as chemical genetics, which enabled them to turn on activity specifically in mice’s microglia. The researchers activated microglia when the mice were trapped in a specific type of environment. The mice later avoided this type of environment, which the researchers interpreted as showing the animals did not like the experience. The mice also became less interested in a sweet lotion, which they usually find very tempting.
In order to verify whether microglia is an important link between the immune system and mood, the researchers investigated what happened when the microglia was inhibited. When the microglia was not available for activation, the mice did not feel weak, even when infected. This reinforces the idea that these cells are essential for the process.
Our results show that activation of microglia is sufficient to create negative mood aversion and mood in mice. Naturally, we would suggest that similar processes occur in many human diseases. It is not unlikely that activated microglia contributes to discomfort and depression in people with inflammatory and neurological diseases, ”says David Engblom.
If further research shows that the biological mechanism described in the study works the same way in humans, it may be possible in the long term to reduce depression symptoms by inhibiting this mechanism.
The study was funded with support from, among others, the Swedish Research Council, the Knott and Alice Wallenberg Foundation, the Swedish Brain Foundation, the Stiftelsen för Parkinsonforskning i Linköping Foundation, the Lars Hierta Memorial Foundation, and the Östergötland region.
Article: “Microglia activation elicits a negative emotional state through prostaglandin-mediated modification of striated neurons”, Anna M. Yarula, Johan Jacobson, Juan Hidalgo, Marcus Hilleg, Antonello Ponce and David Enblum, immunityPosted online on January 20, 2021, doi: 10.1016 / j.immuni.2020.12.016