P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis

Autor: Alazne Zabala, Nuria Vazquez‐Villoldo, Björn Rissiek, Jon Gejo, Abraham Martin, Aitor Palomino, Alberto Perez‐Samartín, Krishna R Pulagam, Marco Lukowiak, Estibaliz Capetillo‐Zarate, Jordi Llop, Tim Magnus, Friedrich Koch‐Nolte, Francois Rassendren, Carlos Matute, María Domercq
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 10, Iss 8, Pp 1-20 (2018)
Druh dokumentu: article
ISSN: 20170874
1757-4676
1757-4684
DOI: 10.15252/emmm.201708743
Popis: Abstract Microglia survey the brain microenvironment for signals of injury or infection and are essential for the initiation and resolution of pathogen‐ or tissue damage‐induced inflammation. Understanding the mechanism of microglia responses during pathology is hence vital to promote regenerative responses. Here, we analyzed the role of purinergic receptor P2X4 (P2X4R) in microglia/macrophages during autoimmune inflammation. Blockade of P2X4R signaling exacerbated clinical signs in the experimental autoimmune encephalomyelitis (EAE) model and also favored microglia activation to a pro‐inflammatory phenotype and inhibited myelin phagocytosis. Moreover, P2X4R blockade in microglia halted oligodendrocyte differentiation in vitro and remyelination after lysolecithin‐induced demyelination. Conversely, potentiation of P2X4R signaling by the allosteric modulator ivermectin (IVM) favored a switch in microglia to an anti‐inflammatory phenotype, potentiated myelin phagocytosis, promoted the remyelination response, and ameliorated clinical signs of EAE. Our results provide evidence that P2X4Rs modulate microglia/macrophage inflammatory responses and identify IVM as a potential candidate among currently used drugs to promote the repair of myelin damage.
Databáze: Directory of Open Access Journals
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