Figure 3.

ARN23746 Rescues Cognitive Impairment in the Ts65Dn Mouse Model of Down Syndrome with no Diuretic Effect

(A) Schematic cartoon of the experimental protocol for the treatment of adult WT and Ts65Dn mice to assess the diuretic effect.

(B) Quantification of the mean ± SEM and single animal cases of the urine volume collected for 120 min after mice were treated with the indicated drugs (two-way ANOVA, F_{treatment (2,69)} = 10.516, p < 0.001,Tukey’s post hoc test, ∗p < 0.05, ∗∗p < 0.01).

(C) Schematic cartoon of the experimental protocol for the treatment of adult WT and Ts65Dn mice with ARN23746 for in vivo efficacy assessment of improved cognitive impairment in DS mice.

(D) Top, schematic representation of the T-maze test. Bottom, quantification of the mean ± SEM and single animal cases of correct choices in mice treated with the indicated drugs (two-way ANOVA, F_{interaction (1,46)} = 5.475, p = 0.024, Tukey’s post hoc test, ∗∗p < 0.01, ∗∗∗p < 0.001).

(E) Top, schematic representation of the OL test. Bottom, quantification of the mean ± SEM and single animal cases of discrimination index in mice treated with the indicated drugs (two-way ANOVA, F_{interaction (1,45)} = 15.523, p < 0.001, Tukey’s post hoc test; ∗∗∗p < 0.001).

(F) Top, schematic representation of the NOR task. Bottom, quantification of the mean ± SEM and single animal cases of the discrimination index in mice treated with the indicated drugs (two-way ANOVA, F_{treatment (1,46)}= 7.154, p = 0.010, Tukey’s post hoc test, ∗ p < 0.05, two-way).

(G) Top, schematic representation of the CFC test. Bottom, quantification of the mean ± SEM and single animal cases of the freezing response in mice treated with the indicated drugs (two-way ANOVA on Ranks, F_{treatment (1,45)}= 4.425, p = 0.041, Tukey’s post hoc test, ∗ p < 0.05, ∗∗p < 0.01). See also Figure S2; Table S4.