Gpr17 regulates oligodendrocyte apoptosis and Xaf1 expression through the cAMP and PKA signaling pathways. A, Relative cAMP levels in cultured OPCs overexpressing Gpr17 or transfected with control vector for 48 h and treated with 10 nm MDL29951 or vehicle for 5 min as indicated. *p < 0.05, **p < 0.01, ***p < 0.001, one-way ANOVA with Tukey's multiple-comparison test. B, Expression of Xaf1 in total RNA from oligodendrocytes overexpressing Gpr17 or transfected with control vector. Primary rat OPCs were transfected and treated with 0.5 mm dibutyryl cAMP or vehicle as indicated in the differentiation medium for 48 h. Data are means ± SEM from three independent experiments. ***p < 0.001, one-way ANOVA with Tukey's multiple-comparison test. C, Western blot analyses of phosphorylated PKA in oligodendrocytes treated with vehicle DMSO, 10 μm pranlukast, or 0.5 mm dibutyryl cAMP in the differentiation medium for 48 h. D, Relative numbers of viable OPCs treated with vehicle or 10 μm pranlukast and the indicated concentration of H89 for 48 h. Data are means ± SEM from three independent experiments. **p < 0.01, ***p < 0.001, one-way ANOVA with Tukey's multiple-comparison test. E, Expression of Xaf1 in the total RNA from oligodendrocytes treated with 10 μm H89 or 0.5 mm KT5720 in the differentiation medium for 48 h. Data are means ± SEM from three independent experiments. *p < 0.05, ***p < 0.001, Student's t test. Veh, Vehicle; Pran, pranlukast; MDL, MDL29951; db-cAMP, dibutyryl cAMP; KT, KT5720.