| First Author | Zabala A | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 8 | PubMed ID | 29973381 |
| Mgi Jnum | J:289188 | Mgi Id | MGI:6434646 |
| Doi | 10.15252/emmm.201708743 | Citation | Zabala A, et al. (2018) P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. EMBO Mol Med 10(8) |
| abstractText | 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. |
