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Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Figure 6

TC-2153 improves cognitive deficits in 3xTg-AD mice.

WT and 3xTg-AD mice (male, 6 mo old) were treated with vehicle or TC-2153 (10 mg/kg, i.p.) and tested in the Y-maze, NOR, and MWM tasks. (A and B) Y-maze, number of arm entries and percentage spontaneous alternations were calculated (*p<0.05, paired t test, AD-TC versus AD-Veh) (WT, n = 20/group; AD, n = 11/group). (C) NOR, the DI of each group was calculated (***p<0.001, AD-TC versus AD-Veh) (WT, n = 9/group; AD, n = 16/group). (D) MWM, the 3xTg-AD mice injected with vehicle (n = 6) showed longer escape latency before finding the hidden platform (3 trials/day; 60 s; 30 m intertrial interval) when compared to AD mice treated with TC-2153 (n = 7) or WT mice injected with vehicle (n = 12) or TC-2153 (n = 13) (three-way ANOVA). * and + represents a statistical significant variation between AD-Veh mice and AD-TC or WT-Veh, respectively. (E) Swim speed at each training day was not significantly different between groups (three-way ANOVA). (F) Number of entries in a circular zone positioned around the previous platform location and in the opposite quadrants. * represents a statistical significant variation between AD-TC mice and other groups for the target quadrant. + indicates a difference for the target and opposite quadrant within each group. Data are mean ± s.e.m. *,+ p<0.05; **,++ p<0.01; ***,+++ p<0.01.

Figure 6