DAPT reverses cognitive deficits in 4-month-old Ts65Dn mice in the Morris water maze.

<p>DAPT was administered to Ts65Dn and control mice (100 mg/kg/day) two days prior to, and throughout, the maze testing. (A) Hidden platform test, latency to reach platform during training. (B) Probe trial on day 12, number of platform crossings. (C) Visible platform test, latency to reach platform. (D) Thigmotaxis. Statistical Analysis: n = 6 for all groups (A–D). (A) 2-way ANOVA with repeated measures revealed a main effect of genotype F1,20 = 11.31, p = 0.003 & Day F10,200 = 4.90, p = 3.00E-06 and an interaction between genotype and DAPT F1,20 = 7.73, p = 0.012. Post-hoc planned comparison test between Ts65Dn+vehicle and all 3 other groups (Ts65Dn+vehicle vs. Ts65Dn+DAPT p = 0.02, Ts65Dn+vehicle vs. control+vehicle p = 0.0003, Ts65Dn+vehicle vs. control+DAPT p = 0.008, n = 6 in all groups for all figures). (B) 2-way ANOVA for number of target platform crossings revealed an interaction between genotype and DAPT F1,20 = 8.46, p = 0.009. Post-hoc planned comparison test revealed a significant difference between Ts65Dn+vehicle vs. Ts65Dn+DAPT p = 0.01 and between Ts65Dn+vehicle vs. control+vehicle p = 0.007. No significant differences were observed for number of crossings of the analogous, virtual opposite platform location (not shown). (C) 2-way ANOVA with repeated measures revealed significant effects of genotype, F1,20 = 9.91, p = 0.005 and day, F10,200 = 21.42, p = 0.001, as well as a significant interaction between genotype and DAPT, F1,20 = 5.43, p = 0.03. Post-hoc planned comparison test revealed significant differences between Ts65Dn+vehicle vs. all 3 other groups (vs. Ts65Dn+DAPT p = 0.04, vs. control+vehicle p = 0.003, and vs. control+DAPT p = 0.005). (D) 2-way ANOVA with repeated measures revealed main effects of genotype, F1,20 = 5.13, p = 0.03 & day F10,200 = 21.94, p<1.00E-06 with an interaction between genotype and DAPT, F1,20 = 5.43, p = 0.03. Post-hoc planned comparison test revealed only a significant difference between Ts65Dn+vehicle vs. control+vehicle p = 0.004.