Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination

Autor: Ronzano, R., Roux, T., Thetiot, M., Aigrot, M. S., Richard, L., Lejeune, F. X., Mazuir, E., Vallat, J. M., Lubetzki, C., Desmazières, A.
Přispěvatelé: Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Gestionnaire, HAL Sorbonne Université 5, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nature Communications
Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-25486-7⟩
Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021)
Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-25486-7⟩
ISSN: 2041-1723
Popis: Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct site of interaction between microglia and axons, in both mouse and human tissues. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglia-node interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Altered axonal K+ flux following demyelination impairs the switch towards a pro-regenerative microglia phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron interaction, that may participate in microglia-neuron communication mediating pro-remyelinating effect of microglia after myelin injury.
Microglia are important for brain homeostasis and plasticity. The mechanisms underlying microglia-neuron interactions are still unclear. Here, the authors show that microglia preferentially interact with the nodes of Ranvier along axons. This interaction is modulated by neuronal activity and contributes to remyelination in mice.
Databáze: OpenAIRE
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