Potentiation of P2X4R favors remyelination and ameliorates EAE

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Potentiation of P2X4R favors remyelination and ameliorates EAE Potentiation of P2X4R favors remyelination and ameliorates EAE ALeft, neurological score of EAE (n = 5) and ivermectin (IVM)‐treated EAE mice (1 mg/kg) (n = 5 mice/group; one representative experiment of two independent experiments). Right, axon conduction latency in the corticospinal tract of control and vehicle‐ and IVM‐treated EAE mice. Symbols indicate significance versus control (*) or versus EAE (#).BEffect of IVM (3 μM)‐ on lysolecithin (LPC)‐induced demyelination in cerebellum organotypic slices, as analyzed by MBP densitometry (n = 5).CStaining for iNOS (red) and MRC1 (green) in control and differently activated microglia in the absence or presence of IVM (3 μM) (n = 3). Scale bar = 50 μm. Symbols indicate significance versus control (*) or versus anti‐inflammatory microglia (#).DqPCR quantification of pro‐inflammatory genes (Ccl2 and Nos2) and anti‐inflammatory genes (Arg1 and Mrc1) in different activated microglia in the absence or presence of IVM (3 μM) (n = 3). Symbols indicate significance versus control (*) or versus pro‐/anti‐inflammatory microglia (#).EControl, pro‐inflammatory, and anti‐inflammatory microglia endocytosis (1 h) of Alexa 488‐labeled myelin in the absence or presence of IVM (3 μM) plus ATPγS (10 μM) (n = 4). Scale bar = 40 μm. Symbols indicate significance versus control (*) or between IVM + ATPγS‐treated and non‐treated cells (#).FMyelin degradation at 6 days, expressed as fold change versus control microglia at the same chase time, in the absence and in the presence of IVM (3 μM) + ATPγS (10 μM) (n = 4).GWithdrawal threshold (grams) of mechanical stimulation by von Frey filaments applied to the mouse hind paw in non‐treated (n = 6) and IVM‐treated mice (n = 7) at specific stages of EAE progression.Data information: Data are presented as mean ± s.e.m. Statistics were performed with Mann–Whitney U‐test (neurological score), one‐way ANOVA (A, D, E, F), and Student's t‐test (B, C). */#P < 0.05, **/##P < 0.01, ***P < 0.001.Source data are available online for this figure. Alazne Zabala et al. EMBO Mol Med. 2018;emmm.201708743 © as stated in the article, figure or figure legend