Figure 1.

PEL24-199 restores short- and long-term spatial memory in APP/PS1 mice. (A) Time representation of APP/PS1 mice treatment and behavioral testing. The mice were treated for four months starting at eight months old, with 1 mg/kg of PEL24-199. Behavioral tests (Actimetry, Elevated Plus Maze, Y-Maze, and Barnes test) were performed at eleven months old, and the mice were sacrificed at twelve months old. (B) Locomotion and motricity tests of untreated versus PEL24-199-treated WT and APP/PS1 animals. Histograms represent the means ± SEM of the distance moved during 10 min. (C) Anxiety test of untreated versus PEL24-199-treated WT and APP/PS1 animals. Histograms represent the means ± SEM of the time spent in the open arms (triangle) versus the closed arms (dots and hatched bars). (D) Short-term memory test of untreated versus PEL24-199-treated WT and APP/PS1 animals. Histograms represent the means ± SEM of the time spent in the new arm (triangle) versus the other arm (dots and hatched bars). (E,F). Learning phase of the long-term memory test between Day one and Day four of untreated versus PEL24-199-treated WT and APP/PS1 animals, as indicated by the total latency and the number of total mistakes needed to find the target hole. (G). Long-term spatial memory was assessed 72 h after the last day of the learning phase. Results represent the percentage of time spent in the target quadrant versus non-target quadrants (others). WT mice (both treated with water or PEL24-199) spent significantly more time in the target quadrant, indicative of a preserved spatial memory. While APP/PS1 mice exhibited spatial memory deficits, as underlined by their lack of preference for the target quadrant, PEL24-199-treated APP/PS1 mice behaved as WT mice, suggesting that the treatment rescued the memory impairment. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, and ns as not significant. using Two-way ANOVA; n = 8–12 per group.