Fig. 5

L41 treatment improves synaptic plasticity and prevents behavioral deficits in APP/PS1 mice. a, b Long-term potentiation (LTP) was induced by delivering theta-burst stimulations to hippocampal CA3-CA1 synapses after 20 min of baseline recordings. Slices from vehicle-treated APP/PS1 mice exhibited deficits in LTP expression relative to littermates. The magnitude of LTP observed in L41-treated APP/PS1 mice was higher than that in vehicle-treated APP/PS1 mice, but lower than in littermates. b Summary bar graph showing the average potentiation represented as the percentage from 30 to 60 min after theta-burst stimulation. Slices from vehicle-treated APP/PS1 mice showed a mean deficit of LTP (137.7 ± 0.163) relative to that of littermates (153.5 ± 0.211) (One-way ANOVA, p < 0.0005). The mean LTP of L41-treated APP/PS1 mouse slices (146.8 ± 0.243) was higher than that of vehicle-treated APP/PS1 mice (One-way ANOVA, p < 0.0005), but lower than that of littermates (One-way ANOVA, p < 0.0005). n = number of slices, N = number of mice. Significant differences between littermates and APP/PS1 injected with vehicle are indicated by *** p < 0.0005. Significant differences between vehicle- and L41-treated APP/PS1 mice are indicated by ^###p < 0. (c, d, e) Spatial learning and long-term memory were evaluated using the Morris water maze paradigm on littermates (n = 12), vehicle- (n = 7) and L41- (n = 7) treated APP/PS1 mice. c Representative occupancy plots during acquisition show a more random search strategy for vehicle- than L41-treateted APP/PS1 mice and littermates. d Escape latency of vehicle-treated littermate controls or vehicle- or L41-treated APP/PS1 mice. The time to reach the platform was different between the groups (Two-way ANOVA: Group effect: F2.110 = 3.68, p = 0.028; Time effect: F4.110 = 7.23, p < 0.0001; Group x Time interaction: F8.110 < 1, ns). Vehicle-treated APP/PS1 mice were impaired relative to vehicle-treated littermate controls (p = 0.02). L41-treated APP/PS1 mice were statistically indistinguishable from littermate controls (p = ns). Significant differences between littermates and vehicle-treated APP/PS1 mice are indicated by ^*p < 0.05. e Probe trial performance at 72 h. (Two-way ANOVA, Group effect: F2.46 = 1.315, p = ns; quadrant effect: F1.46 = 12.58, p = 0.009; Group x quadrant interaction effect: F2.46 = 5.27, p = 0.0087). Vehicle-treated APP/PS1 mice were impaired relative to vehicle-treated littermates (p < 0.05). L41 treatment rescued this memory impairment (p < 0.005), confirmed by a preference for the trained target quadrant. Target quadrant (TQ) and other quadrants (OQ). Bottom: representative occupancy plots during 72 h-probe test show a random search strategy for vehicle-treated APP/PS1 mice, in contrast to both vehicle-treated littermates and L41-treated APP/PS1 mice. Significant differences between the groups are indicated by *p < 0.05 and ** p < 0.005. Significant differences between the quadrants are indicated by ^#p < 0.05 and ^## p < 0.005. Data represent the mean ± SEM and were analyzed by one-way or two-way ANOVA followed by Tukey’s post hoc test. f Working memory was evaluated using the Y-maze paradigm in littermates (n = 9) and vehicle- (n = 8), or L41- (n = 5) treated APP/PS1 mice. The distance covered by the mice in the arms during the evaluation phase was different between each arm (Two-way ANOVA: Group effect: F2.19 = 1.232; ns; Arm effect: F1.19 = 15.31, p < 0.005; Group x Arm interaction: F2.19 = 1 .232, ns). Vehicle-treated APP/PS1 mice did not cover significantly more distance in the NA (new arm) than the OA (other arms, including starting and familiar arms) (Two-way ANVOVA, ns). Littermates and L41-treated APP/PS1 mice covered more distance in the new arm than in the other arms (p < 0.05 for both). Significant differences between distance covered in the arms are indicated by ^# p < 0.05