Figure 4.
FGFRs mediate the effects of EE on neurogenic cell expansion. All mice are of the same genotype (Nestin-CreERT2;Fgfr1fx/fx;Fgfr2fx/fx;Fgfr3fx/fx) and were administered either tamoxifen (Tam; +) or vehicle corn oil (–). A–G, Experimental timeline (A) for B–G. B–E, Immunostains of the DG of control (Ctrl; B, D) and Fgfr-3KO (C, E) mice in home cages (HCs; B, C) or EE (D, E). BrdU, White; DCX, red; DAPI, blue. Scale bar, 50 µm. F, Number of BrdU+DCX+ for mice in home cages (blue) or EE (red). Main effect of housing: F(1,29) = 127.1, p < 0.0001; main effect of genotype: F(1,29) = 39.97, p < 0.0001; interaction: F(1,29) = 39.36, p < 0.0001; ****p < 0.0001, **p = 0.0065 and 0.0086. G, Number of DCX+ immature neurons/late progenitor. Main effect of housing: F(1,29) = 91.94, p < 0.0001; main effect of genotype: F(1,29) = 1.171, p = 0.2882; interaction: F(1,29) = 0.8057, p = 0.3768; ****p < 0.0001. H–O, Experimental timeline (H) for I–O. I–L Immunostains of the DG of control (I, K) and Fgfr-3KO (J, L) mice in home cages (I, J) and EE (K, L). BrdU, White; DCX, red; GFAP, green; DAPI, blue. Scale bar, 50 µm. M, Number of BrdU+DCX– RGL/early progenitor cells. Main effect of housing: F(1,63) = 2874, p < 0.0001; main effect of genotype: F(1,63) = 8.604, p = 0.0047; interaction: F(1,63) = 2.366, p = 0.1290; *p = 0.0179, **p = 0.0012, ***p = 0.0002, ****p < 0.0001. N, Number of DCX+ cells. Main effect of housing: F(1,63) = 93.86, p < 0.0001; main effect of genotype: F(1,63) = 22.16, p < 0.0001; interaction: F(1,63) = 1.749, p = 0.0001; *p = 0.0111, ****p < 0.0001. O, Number of BrdU+DCX+ cells. Main effect of housing: F(1,63) = 28.26, p < 0.0001; main effect of genotype: F(1,63) = 13.39, p = 0.0005; interaction: F(1,63) = 0.1461, p = 0.7036; **p = 0.0028, 0.0013, and 0.0038, ****p < 0.0001. Each circle represents a mouse. Numbers of mice are indicated in each bar. Values are the mean ± SEM, using two-way ANOVA with Tukey's post hoc test.