Fig. 5
Behavior tests demonstrated that A40-PO treatment improved the performance of APP/PS1 mice. Morris water maze test in which mice were injected with saline (sham APP/PS1 group and WT group, 200 μL) or A40-POs (APP/PS1 POs group, 10 g/L 200 μL) once daily for the 365th–367th morning of their lifespan. Recovery was executed for 1 week under the original rearing conditions. The place navigation test (Stage I) was performed on days 375th–378th, and the results revealed a gradual decrease in passing length and escape latency for finding the platform in all groups, with the APP/PS1 POs group matching the WT group and significantly outperforming the Sham APP/PS1 group. During the spatial probe test (Stage II), both the APP/PS1 POs and WT groups demonstrated more passing times and a greater percentage of time spent at the platform’s original location. In the reverse-place navigation (Stage III) trial from days 380th–383rd, with the platform moving to the opposite side, the APP/PS1 POs and WT groups initially took longer, indicating stronger spatial memory from Stage I and Stage II. Their reverse passing length and escape latency decreased rapidly over time and were significantly lower than those of the Sham APP/PS1 mice at the last day of this stage. On day 384th, in the reverse spatial probe (stage IV) test without the platform, A40-POs treated mice still outperformed the Sham APP/PS1 group. After 180 days, the mice were reperformed for place navigation and spatial probes (Stages V and VI). The conditions were consistent with those of stage I and stage II. Six months after the injection of A40-POs, the mice could still find the escape platform within a shorter time in the navigation experiment. They stay longer and traverse more times at the correct location in the spatial probe test. The performance of the mice injected with A40-POs (6 months p.i.) was close to that of the wild-type mice with same age, and better than that of the Sham APP/PS1 group (a). Place navigation trials (Stages I, III and V) were analyzed via two-way ANOVA, whereas spatial probe trials (Stages II, IV, and VI) were compared via one-way ANOVA. Significance levels are denoted as *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, with n ≥ 11 (for all 12-month-old mice) and n ≥ 6 (for all 18-month-old mice). Nest-construction images (b), nest scores (c) and sucrose preferences (d) were recorded for the APP/PS1 Sham, APP/PS1 POs and wild-type groups at two time points post-injection. (groups were compared via one-way ANOVA. Significance levels are denoted as *p < 0.05, **p < 0.01, ***p < 0.001 with n = 5, the data are presented as the means ± SEMs.)
