Increased Sox2+ and PSA-NCAM+ cells in the SVZ of mice with genetic or pharmacological inhibition of p53 in vivo after cuprizone-induced demyelination. A, Confocal image of brain sections from adult p53+/+mice receiving a 4 week control diet or a 0.2% cuprizone diet in the absence (cup) or presence of systemic administration of pifithrin-α (cup+pif). Sections were stained with antibodies against Sox2 (green) and DAPI (blue). The bar graphs represent the number of Sox2+ cells counted in coronal sections at the level of the dorsal corpus callosum of at least three mice per group. **p < 0.01; *p < 0.05. Note the wider distribution of the Sox2+ cells in mice treated with cuprizone compared with controls and the greater response detected in the animals treated with pifithrin-α. B, Confocal image of brain sections from untreated (control diet) or cuprizone-treated (cup) p53−/− adult mice stained with antibodies against Sox2 (green) and DAPI (blue). The bar graphs represent the number of Sox2+ cells. Also in this case, cuprizone treatment significantly increased the number of Sox2+ cells in the SVZ of p53−/− mice. *p < 0.05. Note the greater number observed in these mice compared with wild type (A). C, Confocal image of PSA-NCAM+ cells in the adult SVZ of p53+/+ mice receiving a 4 week control diet or a 0.2% cuprizone diet in the absence (cup) or presence of systemic administration of pifithrin-α (cup+pif). Sections were stained with antibodies against PSA-NCAM (red) and DAPI (blue). The bar graphs represent the number of PSA-NCAM+ cells counted in the SVZ at the level of the dorsal corpus callosum of at least three mice per group. **p < 0.01; ***p < 0.001. Note that the combination of cuprizone and pifithrin-α had a stronger effect on the number of PSA-NCAM+ cells than cuprizone alone. D, Confocal image of PSA-NCAM+ (red) cells in the adult SVZ of p53−/− mice untreated (control diet) or after 4 weeks of cuprizone diet (cup). Note that the number of PSA-NCAM+ cells is already elevated in untreated controls and that after cuprizone stimulation it increases to levels that are comparable with those detected in the pifithrin-treated wild-type animals. Scale bar, 50 μm. Error bars indicate SEM. V, Ventricle.