Neurological disorders represent a growing burden on society, while therapeutic opportunities are limited. Recent research has highlighted the important role of inflammatory mechanisms in the development and progression of common brain disorders. Our project focuses on the mechanisms through which microglia, the main inflammatory cells of the central nervous system contribute to normal brain function and neuronal injury. We have identified a novel form of interaction between microglia and neurons, which appears particularly important for microglial monitoring of neuronal activity and for microglia-mediated actions shaping neuronal fate in health and disease. We have revealed some of the main molecular pathways that contribute to the formation and maintenance of these structures named somatic microglial junctions, which are very common in both the mouse and the human brain. Blockade of microglial junction formation leads to increased neuronal loss after acute brain injury induced by stroke. We reveal that these compartment-specific microglia-neuron interactions are already essential for developing neurons and show major changes in different forms of brain disorders and in old age. In line with this, we show that microglia also interact with different cell types around cerebral blood vessels and regulate cerebral blood flow in both the healthy and the injured brain. The contribution of microglial inflammatory responses to limiting the spread of viral infections in the brain and to the maintenance of chronic pain have also been revealed. Collectively, our data suggest that via targeted modulation of microglial responses it may be possible to shape the outcome of diverse neurological disorders. Further research is required to understand the complex interactions between microglia, neurons and blood vessels that are influenced by diverse inflammatory processes. These efforts may facilitate the development of novel therapeutic strategies to treat neurological disorders.
