Fig. 1.

Oral administration of OLT1177 in APP/PS1 animals for 3 mo restores cognitive deficits. (A) The treatment of either OLT1177 (3.75 g/kg and 7.5 g/kg; drug per kilogram feed) or control food was started at the age of 6 mo and continued for 3 mo. (B and C) During the treatment period, neither WT nor APP/PS1 mice show differences in weight (n = 16 to 33 animals). (D) WT and APP/PS1 mice indicate a learning behavior during the training phase of the spatial learning test. APP/PS1 mice show higher escape latency during acquisition on day 5 compared to WT mice (day 5 P = 0.037; n = 7 to 12 animals). (E) Moreover, on days 3 and 5 the APP/PS1 mice show increased escape latency compared to APP/PS1 mice treated with 7.5 g/kg OLT1177 (day 3 P = 0.001; day 5 P = 0.007). (F) WT mice and APP/PS1 mice treated with 7.5 g/kg OLT1177 display a significant preference for the TQ, whereas the APP/PS1 mice with control or low dose food did not show any preference (NT vs. TQ: WT P < 0.001; APP/PS1 P > 0.99; APP/PS1 3.75 g/kg P = 0.39; APP/PS1 7.5 g/kg P < 0.001; WT vs. APP/PS1 P = 0.001; WT vs. APP/PS1 3.75 g/kg P = 0.014; WT vs. APP/PS1 7.5 g/kg P = 0.68; APP/PS1 vs. APP/PS1 7.5 g/kg P = 0.0088). (G) WT animals treated with control food, low-dose, or high-dose OLT1177 did not show any differences between the groups. (H) The heat maps of pooled animals manifest the results of the reference test (scale: blue 0 s to red 1.9 s, n = 3 to 4 animals). Data are presented as mean ± SEM. *P < 0.05, ***P < 0.001 compared to WT, ⁺⁺P < 0.01, ⁺⁺⁺P < 0.001 compared to APP/PS1 CTRL, ^P < 0.05, ^^^P < 0.001 compared to NT.