MICROGLIA have been shown in previous research to be activated in several neurological diseases, including Parkinson’s disease and Alzheimer’s disease. Patients with such neurological diseases often report a negative mood, which researchers from Linköping University, Linköping, Sweden, have determined in a recent study is contributed to by microglia.
The role of inflammation in depressive symptoms and disorders has been suggested by numerous researchers, but the exact mechanism is not yet known. The researchers from Linköping University used bidirectional chemogenetic manipulations, which enabled them to alter the activity of the microglia specifically. Through controlling the microglial activity in mice, they were able to investigate how microglial signalling regulates mood. They found that local cytokine expression and a negative affective state, characterised by anhedonia and aversion, was induced when microglia were activated in the dorsal striatum.
Additionally, they explored the role of microglia in the link between the immune system and mood by inhibiting microglial cells. When the microglial cells were inactivated, aversion induced by systemic inflammation was blocked. Two signal molecules, IL-6 and prostaglandin E2, were identified to be crucial to the inflammation-induced aversion, on which lead author Prof David Engblom commented: “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.” Finally, a reduction in the excitability of striatal neurons was induced by microglial activation, which was prostaglandin dependent.
“Our results show that the activation of microglial cells is sufficient to create aversion and negative mood in mice,” said Prof Engblom. He noted that it is not far reaching to suggest that similar processes take place in several human diseases, and therefore that activated microglia contribute to depressed mood in people with inflammatory and neurological diseases. If further research confirms this mechanism in humans, it will provide a much-needed new drug target for hard-to-treat depressive symptoms and disorders.