ACE2-deficient mice (ACE2) reveal no running-induced neurogenesis. a The number of proliferating cells in running animals and sedentary controls (baseline) was quantified on day 7, 24 h after the first of three i.p. BrdU injections. b At baseline, no changes in the absolute number of BrdU-positive cells were observed between WT and ACE2. However, voluntary wheel running robustly increased proliferation in WT with no effect on ACE2. One-way ANOVA F(3,19) = 51.36, p < 0.0001; followed by Tukey’s post hoc test, ***p < 0.001 indicates statistical significance relatively to sedentary WT control, ###p < 0.001 between WT and ACE2 for the same condition; data are presented as mean ± SEM. c ACE2 ran significantly shorter distances than WT. Unpaired Student’s t test, ##p < 0.01. d Running significantly shorter distances than their WT controls (Unpaired Student’s t test, **p < 0.01, e), WTRUN1/2 mice revealed the same robust increase in BrdU-positive cells. One-way ANOVA F(2.9) = 28.09, p = 0.0001; followed by Tukey’s post hoc test, **p < 0.01 indicates statistical significance relatively to sedentary WT control. f Representative images of peroxidase staining of BrdU-positive cells in the subgranular zone (SGZ) for baseline and running in WT and ACE2; scale bar 100 µm. g Running robustly induced the number of cells co-expressing either BrdU/Sox2 (type-2a) or BrdU/DCX (type-2b/3) in the adult dentate gyrus of WT. No increase in these cell types occurred in ACE2. The number of BrdU/GFAP type-1 cells did not change between conditions and genotypes. One-way ANOVA Ftype-1(3,12) = 0.686, p = 0.5173, Ftype-2a(3,13) = 30.10, p < 0.0001, Ftype-2b/3(3,13) = 0.686, p < 0.0001; followed by Tukey’s post hoc test, ***p < 0.001 indicates statistical significance relatively to sedentary controls of the same genotype, ###p < 0.001 between WT and ACE2 for the same condition. The table represents BrdU phenotype distribution in percentage; data are presented as mean ± (SEM), **p < 0.01, ***p < 0.001 relatively to sedentary WT control, ###p < 0.001 between WT and ACE2 for running conditions