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Bidirectional Microglia-Neuron Communication in Health and Disease


Bidirectional Microglia-Neuron Communication in Health and Disease

Zsuzsanna Szepesi et al. Front Cell Neurosci.


Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult to the CNS homeostasis. Although microglia have long been recognized as a crucial player in generating and maintaining inflammatory responses in the CNS, now it has become clear, that their function are much more diverse, particularly in the healthy brain. The innate immune response and phagocytosis represent only a little segment of microglia functional repertoire that also includes maintenance of biochemical homeostasis, neuronal circuit maturation during development and experience-dependent remodeling of neuronal circuits in the adult brain. Being equipped by numerous receptors and cell surface molecules microglia can perform bidirectional interactions with other cell types in the CNS. There is accumulating evidence showing that neurons inform microglia about their status and thus are capable of controlling microglial activation and motility while microglia also modulate neuronal activities. This review addresses the topic: how microglia communicate with other cell types in the brain, including fractalkine signaling, secreted soluble factors and extracellular vesicles. We summarize the current state of knowledge of physiological role and function of microglia during brain development and in the mature brain and further highlight microglial contribution to brain pathologies such as Alzheimer's and Parkinson's disease, brain ischemia, traumatic brain injury, brain tumor as well as neuropsychiatric diseases (depression, bipolar disorder, and schizophrenia).

Keywords: cytokines; extracellular vesicles; fractalkine; microglia; neurodegeneration; neuroinflammation; neuron.


Bidirectional signaling between microglia (green) and neuron (purple). Neuron–microglia communication is mediated by receptor–ligand interactions as well as by various soluble factors. Microglia are equipped with a group of surface receptors, which trigger signals and regulate specific microglia function like phagocytosis, motility and viability. Many of the receptor ligands, such as CX3CR1, CD200R, and CD172a are released or expressed on the surface of neurons. Receptor–ligand interactions represent a classical contact dependent communication between microglia and neurons. Microglia and neurons reciprocally release soluble factors that can modulate cell functions and promote tissue homeostasis.
Fractalkine (CX3CR1–CX3CL1) signaling between microglia (green) and neuron (purple) in normal (green square) and pathologic (red square) states. CX3CL1 is either membrane-bound or cleaved by metalloproteinases to become soluble. Membrane bound CX3CL1 is an OFF-signal, that keeps microglia in a surveying state, and soluble CX3CL1 is believed to act as a chemoattractant, stimulating migration of inflammatory cells. Fractalkine signaling has many roles in both healthy and pathologic conditions. Black triangles indicate increase (formula image), decrease (formula image) or not specified (formula image).

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