Neuron-Microglia Interaction in Neuroinflammation

Microglia are monocyte-macrophage lineage cells, while other glial cells are neuroectodermal origin. Accumulation of microglia is commonly observed around degenerating neurons. There, microglia produce a variety of factors and function both neurotoxic and neuroprotective. Thus, accumulation of glia in various neurological disorders is not a static scar, gliosis, but more actively involved in degeneration and regeneration as neuroinflammation. We have shown previously that the most neurotoxic factor from activated microglia is glutamate, and that the suppression of glutamate release from microglia results in amelioration of disease progression in animal models of neurodegenerative disorders. On the other hands, when exposed to harmful stimuli, neurons also produce various factors as “help me” signals. Recently, we found that a CX3C chemokine, fractalkine (FKN), and interleukin-34 (IL-34) were secreted from damaged neurons. FKN and IL-34 differently activated microglia to rescue neurons by upregulating phagocytosis of toxicants or damaged debris, and production of anti-oxidant enzyme. The bi-directional interaction between neurons and microglia is important for understanding of chronic neuroinflammation, and gives us clues for future therapeutic strategy against neurodegenerative disorders.