Figure 3.

Metformin Increases the Absolute Numbers of SE-Derived NPCs in the Brain Parenchyma following Injury

(A) Experimental design for metformin administration and behavioral testing. Lineage tracing of SE-derived cells used Nestin-CreER^T2/R26R-YFP transgenic mice.

(B) Quantification of SE-derived YFP+ cells found in the striatum (n ≥ 3 mice/group, two-way ANOVA), motor cortex (n ≥ 3 mice/group, two-way ANOVA), and corpus callosum (n ≥ 3 mice/group, two-way ANOVA) is shown.

(C) Quantification of YFP+ cells that were co-labeled with NeuN, indicating newborn neurons, in striatum (n ≥ 3 mice/group, two-way ANOVA) and motor cortex (n ≥ 3 mice/group, two-way ANOVA) is shown.

(D) Quantification of YFP+ cells that were co-labeled with Olig2+ or MBP+, indicating newborn immature or mature oligodendrocytes, respectively, in striatum (n ≥ 3 mice/group, two-way ANOVA), motor cortex (n ≥ 3 mice/group, two-way ANOVA), and corpus callosum (n ≥ 3 mice/group, two-way ANOVA) is shown.

(E–G) Coronal sections immunostained for YFP+ cells (green) and Hoechst (blue) (E); YFP+ (green), NeuN (red), and Hoechst (blue) (F); and YFP+ (green), Olig2+/MBP+ (red), and Hoechst (blue) (G) are shown.

(H) The relative percentages of differentiated neurons (striatum and motor cortex) and differentiated oligodendrocytes (striatum, motor cortex, and corpus callosum) were not significantly different between groups. IL and CL hemispheres were pooled together (n ≥ 4 mice/group, t test). Arrows denote labeled cells. Scale bars, 20 μm. Data are presented as mean ± SEM. TAM, tamoxifen; ST, striatum; MC, motor cortex; CC, corpus callosum. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001.

See also Figure S2.