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. 2012 Aug 6;109(42):E2895–E2903. doi: 10.1073/pnas.1121081109

Fig. 3.

Fig. 3.

LEV treatment reverses learning and memory deficits in hAPP mice. hAPPJ20 mice and NTG controls were chronically treated with saline or LEV. (A) Context-dependent learning and memory in an open field arena. In the initial phase of this test, all mice (n = 10–15 mice per genotype and treatment) showed habituation to the novel environment, reaching similar levels of activity on the fourth trial (no treatment or genotype effects and no interaction by two-way repeated-measures ANOVA). However, when reintroduced into the same arena 7 d later, saline-treated, but not LEV-treated, hAPP mice showed clear evidence of abnormal dishabituation (forgetting) compared with the control groups (P = 0.045 for interaction between genotype and treatment on trial 5 by two-way ANOVA). P < 0.005 vs. LEV-treated hAPP mice, P < 0.0005 vs. saline-treated NTG mice (Bonferroni test). Saline-treated hAPP mice were the only group that showed dishabituation in the open field 7 d after the fourth trial (P = 0.006 by paired t test, comparing total movements in trial 4 vs. trial 5). (B) Spatial learning and memory index (ratio of total movements during trials 4 and 5). Two-way ANOVA revealed a significant interaction between genotype and treatment (P = 0.0031). ***P < 0.0005 vs. saline-treated NTG (Bonferroni test). (C) Learning curves during spatial training in the Morris water maze (n = 10–15 mice per genotype and treatment). The distance each mouse swam to reach the hidden platform was recorded during 5 d. Data points represent the average performance of mice during four training trials/d. Repeated-measures ANCOVA revealed a significant interaction between genotype and day in saline-treated NTG and hAPP mice (P = 0.0063) and a significant interaction between LEV treatment and day in hAPP mice (P = 0.022) but not in NTG controls. (D) Twenty-four hours after the last training session, mice were tested in a probe trial (platform removed), and the percentage of time mice spent swimming in the target quadrant was calculated. One-tailed, one-sample t tests were performed to determine if the mean of each group was different from chance (dotted line). *P < 0.05, **P < 0.005, ***P < 0.0005 vs. 25%. Only saline-treated hAPP mice did not show a preference for the target quadrant. Two-way repeated-measures ANOVA revealed a significant interaction between genotype and treatment (P = 0.01). Bonferroni test revealed a significant difference between hAPP/saline and hAPP/LEV (P = 0.05). (E and F) Novel object recognition performed in an independent cohort of mice (n = 9–13 mice per genotype and treatment). (E) Preference index represents the time spent with the novel object (N) divided by the total time spent with both novel (N) and familiar (F) objects. One-tailed, one-sample t tests were performed to determine if the mean of each group was different from chance (dotted line). **P < 0.005, vs. 0.5. (F) Number of times mice interacted with the novel (N) versus the familiar (F) object during a 10-min test session. *P < 0.05, **P < 0.005 vs. familiar object (unpaired t test). Values are means ± SEM.