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Mechanisms and significance of microglia–axon interactions in physiological and pathophysiological conditions

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Abstract

Microglia are the resident immune cells of the central nervous system, and are important for cellular processes. In addition to their classical roles in pathophysiological conditions, these immune cells also dynamically interact with neurons and influence their structure and function in physiological conditions. Microglia have been shown to contact neurons at various points, including the dendrites, cell bodies, synapses, and axons, and support various developmental functions, such as neuronal survival, axon elongation, and maturation of the synaptic circuit. This review summarizes the current knowledge regarding the roles of microglia in brain development, with particular emphasis on microglia–axon interactions. We will review recent findings regarding the functions and signaling pathways involved in the reciprocal interactions between microglia and neurons. Moreover, as these interactions are altered in disease and injury conditions, we also discuss the effect and alteration of microglia–axon interactions in disease progression and the potential role of microglia in developmental brain disorders.

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  1. Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yuki Fujita & Toshihide Yamashita

  2. WPI Immunology Frontier Research Center, Osaka University, 3-1, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yuki Fujita & Toshihide Yamashita

  3. Graduate School of Frontier Bioscience, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshihide Yamashita

  4. Department of Neuro-Medical Science, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshihide Yamashita

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YF performed the literature search and drafted the manuscript. TY had the idea for the article and revised the work.

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Fujita, Y., Yamashita, T. Mechanisms and significance of microglia–axon interactions in physiological and pathophysiological conditions. Cell. Mol. Life Sci. 78, 3907–3919 (2021). https://doi.org/10.1007/s00018-021-03758-1

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