Figure 2.

PLX3397 Treatment Depletes Microglia and Rescues Cognitive Deficits in Dp(16) Mice

(A) Experimental protocol.

(B) Iba1-stained hippocampal slices and highlighted regions from P22 WT and Dp(16) animals treated with either vehicle (top) or PLX3397 (bottom) in the chow. Scale bar: 100 μm.

(C) Quantification of the density of microglial cells. Bars represent the average density of Iba1⁺ cells of all the analyzed animals ± SEM, and symbols represent data points for each animal (1 slice per animal). ^∗∗∗p < 0.001; two-way ANOVA; F_Treatment (1, 29) = 642.6; p < 0.001; Holm-Sidak post hoc test.

(D) Immunoblots on protein extracts from lysates of hippocampi obtained from P22 WT and Dp(16) mice treated with vehicle or PLX3397 (left). Quantification of Iba1 (middle) and NG2 (right) levels normalized to GADPH is shown. Bars represent the average percentage of Iba1 or NG2 over WT vehicle of all analyzed animals ± SEM, and symbols represent data points for each animal. ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.001; ^∗∗∗∗p < 0.0001; for Iba1: two-way ANOVA, F_Treatment (1, 50) = 54.53, p < 0.0001, Holm-Sidak post hoc test. For NG2: two-way ANOVA; F_Treatment (1, 46) = 6.774; p = 0.0126; Holm-Sidak post hoc test.

(E and F) Quantification of the discrimination index in the NOR and OLT tests in P22 WT and Dp(16) mice following vehicle or PLX3397 treatment. Bars represent the average discrimination index of all analyzed animals ± SEM, and symbols (circles, males; triangles, females) represent data points for each animal.

(E) ^∗p < 0.05; ^∗∗p < 0.01; two-way ANOVA; F_Interaction (1, 61) = 13.04; p = 0.0006; Holm-Sidak post hoc test.

(F) ^∗∗∗∗p < 0.0001; two-way ANOVA; F_Interaction (1, 44) = 24.54; p < 0.0001; Holm-Sidak post hoc test.