Fig. 2: NAP treatment increases the relative discrimination between novel and familiar objects, protects social memory and preserves motor function.

For males, animal performance in the behavioral tests is shown (n = 3–15 per experimental group). Data are expressed as mean ( ± SEM) total time (sec) spent exploring all objects/mice designated by relative discrimination index (D2, ‘a’ and ‘b’ - exploration of familiar and novel objects/mice, respectively). a, b For both short and long retention choice phases in males, Two-way ANOVA with Tukey post-hoc test was performed. For short retention choice phase, main genotype (F(1,38) = 4.702, p = 0.036), treatment (F(1,38) = 9.478, p = 0.004) and interaction (F(1,38) = 9.732, p = 0.003) effects were found, with significant differences between Adnp^+/+ and Adnp^+/− mice (***p < 0.001), and between Adnp^+/− and NAP-treated Adnp^+/− mice (***p < 0.001). For long retention choice phase, main genotype (F(1,38) = 9.327, p = 0.004), treatment (F(1,38) = 6.236, p = 0.017) and interaction (F(1,38) = 15.279, p < 0.001) effects were found, with significant differences between Adnp^+/+ and Adnp^+/− mice (***p < 0.001), and between Adnp^+/− and NAP-treated Adnp^+/− mice (***p < 0.001). c In the social recognition test, main effect for sniffed item was found (F(1,39) = 302.179, p < 0.001), with significant differences between sniffing time of the cup (c) and mouse (M) in Adnp^+/+, Adnp^+/−, and NAP-treated Adnp^+/− mice (**p < 0.01), and NAP-treated Adnp^+/− mice (***p < 0.001 vs. cup). Two-way repeated measures ANOVA with group as a fixed factor and sniffed item (e.g., mouse vs. cup) as repeated factor and Tukey post-hoc test was performed. d Adnp^+/− male mice spent less time in exploring the novel mouse, as compared with Adnp^+/+ mice. Treatment with NAP improved social memory for the Adnp^+/− mice. Unpaired Student’s t-test analyses revealed significant differences between vehicle-treated Adnp^+/+ and Adnp^+/− mice, and between NAP- and vehicle-treated Adnp^+/− mice (***p < 0.001). All reported p-values were also significant after multiple comparisons correction at FDR of 10%. e In males, the olfactory function was preserved, and no significant differences were observed between experimental groups. **p < 0.01, ***p < 0.001 vs. previous sniffing (novel vs. familiar odor), paired t-test. For each experimental group, general olfaction ability was measured by calculating area under the curve (AUC)—inset graph. Unpaired Student’s t-test analyses revealed significant differences between vehicle-treated Adnp^+/+ and Adnp^+/− mice, and between NAP- and vehicle-treated Adnp^+/− mice (*p < 0.05). f In the Hanging Wire Test, male Adnp^+/− mice display significant decreased latency to fall, with NAP ameliorating. Unpaired Student’s t-test analyses revealed significant differences between vehicle-treated Adnp^+/+ and Adnp^+/− mice, and between NAP- and vehicle-treated Adnp^+/− mice (**p < 0.01, *p < 0.05). All reported p-values were also significant after multiple comparisons correction at FDR of 10%