Chronic inflammation and activation of microglia in the brain may contribute to the depression that can accompany neurodegenerative conditions, as well as other diseases that feature persistently raised inflammation. Researchers here provide supporting evidence for that hypothesis. Microglia are innate immune cells of the central nervous system, and increased inflammatory behavior and senescence in this cell population is implicated in age-related neurodegeneration. Clearing senescent microglia can reduce inflammation and reverse tau pathology in animal models of tauopathies, for example.
Research has shown that microglial cells are activated in several neurological diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. People who are affected by these conditions also often fall into a negative mood. Other previous research has suggested that inflammatory processes also play a role in the development of depression. This led the researchers behind the new study to examine more closely whether microglial cells are involved in regulating mood during inflammation. "The study showed that animals feel sick and uneasy when we activate the microglial cells. We demonstrate that two signal molecules, interleukin-6 and prostaglandin E2, are particularly important in these processes. It's not surprising that these signal substances are central, but we were a bit surprised that it is the microglial cells that release these molecules."
During inflammation, many processes are initiated in several cell types. One of the challenges in determining the role played by a specific cell type in the body, therefore, is to isolate its effects. In this study, the scientists used a technique known as chemogenetics, which enabled them to switch on the activity specifically in microglial cells in mice. The researchers activated the microglial cells when the mice were being kept in a certain type of surroundings. The mice subsequently avoided this type of surroundings, which the researchers interpret as showing that the animals disliked the experience. The mice also became less interested in a sweet solution, which they normally find very tempting.
In order to investigate whether the microglial cells are an important link between the immune system and mood, the researchers investigated what happened when microglial cells are inhibited. When the microglial cells were not available for activation, the mice did not feel poorly, even when they had inflammation. This reinforces the idea that these cells are necessary for the process. If further research demonstrates that the biological mechanism described in the study functions in the same way in humans, it may be possible in the long run to reduce symptoms of depression by inhibiting this mechanism.