Fig. 2.

LEV treatment reverses behavioral abnormalities in hAPP mice. Behavioral testing was performed in two independent cohorts of 4- to 6-mo-old mice. Because results were similar in both cohorts, the data were pooled. (A and B) Before acute and chronic treatments, mice were prescreened in an open field for 5 min. (A) hAPPJ20 mice were more active than NTG controls (***P < 0.0001 by t test). (B) Within each genotype, mice were divided into two groups, so that baseline activity levels did not differ between groups before treatment with LEV or saline. Two-way ANOVA revealed a significant effect of the genotype (P < 0.0001) but not of group (P = 0.61) and no interaction effect (P = 0.43). ***P < 0.0005 vs. NTG (Bonferroni test). (C–F) hAPP mice and NTG controls were treated chronically with saline or LEV (75 mg⋅kg⁻¹⋅d⁻¹, s.c.; n = 21–30 mice per genotype and treatment). (C) Mice were tested in the open field 8 d (cohort 1) or 19 d (cohort 2) after the treatment started. The numbers of peripheral and central ambulatory movements and of fine movements were measured. Amb., ambulation; Mov., movements. (D–F) Mice were tested in the elevated plus maze 19 d (cohort 1) or 5 d (cohort 2) after the start of treatment. The total distance moved (D), the distance moved in the open arms (E), and the percentage of total time spent in the open arms (F) were measured. Two-way ANOVA revealed a significant interaction between genotype and treatment [C, P = 0.001 (peripheral ambulation); D, P = 0.007; E, P = 0.003; F, P = 0.012] and a significant genotype effect [C, P = 0.001 (central ambulation)]. *P < 0.05, **P < 0.005, ***P < 0.0005 vs. saline-treated NTG or as indicated by bracket (Bonferroni test). Values are means ± SEM.