Fig. 8: Lpc-EV treatment improved cognitive deficits in Tg-APP/PS1 mice.

a Experimental design. Tg-APP/PS1 mice were orally administered Lpc-EV at a dose of 2.27 mg/kg/day from 6.5 months of age (green line) until the end of the behavioral tests. Behavioral tests were performed in the order of the novel object recognition test (NOR), water maze test (WM), and passive avoidance test (PA). b–f The novel object recognition test: The experimental steps in the NOR test (b). Time spent exploring between two identical objects during familiarization (c, familiarization), between a novel and a familiar object 2 h after familiarization (d, NOR-2 h), between a displaced object and a familiar object 15 min later (e, NLR-15 min), and between a novel and a familiar object 24 h after familiarization (f, NOR-24 h) for the indicated groups. n = 8, 9, and 10 for WT, Tg, and Tg+Lpc-EV, respectively. Familiarization; WT, t(14) = 0.8347, p = 0.4179; Tg, t(16) = 1.720, p = 0.1047; Tg+Lpc-EV, t(18) = 0.4314, p = 0.6713. NOR-2 h; WT, t(14) = 3.733, p = 0.0022; Tg, t(16) = 1.686, p = 0.1111; Tg+Lpc-EV, t(18) = 5.516, p < 0.0001. NLR-15 min; WT, t(14) = 3.557, p = 0.0032; Tg, t(16) = 1.283, p = 0.2178; Tg+Lpc-EV, t(18) = 3.561, p = 0.0022. NOR-24 h; WT, t(14) = 3.210, p = 0.0063; Tg, t(16) = 0.8527, p = 0.4064; Tg+Lpc-EV, t(18) = 2.753, p = 0.0131. g–k The water maze test: The latency to find the hidden platform in the hidden platform trial (g) for the indicated groups. Representative tracking (h) and time spent (i) in each quadrant in the probe trial of the indicated groups. The dashed line indicates a 25% chance of exploring a quadrant. C, center; P, periphery; T, target; L, left; R, right; O, opposite. The latency to find the platform during the visual platform trial (j) and swim speed (k) in the visual platform trial of the indicated groups. n = 7 (WT), 8 (Tg), and 10 (Tg+Lpc-EV). Training (g); genotype, F(2,22) = 6.026, p = 0.0079; Lpc-EV treatment, F(4,88) = 51.43, p < 0.0001; interaction, F(8,88) = 1.531, p = 0.1572. Probe trial (i); target, F(2,22) = 4.479, p = 0.0233. Latency (j), F(2,21) = 0.2587, p = 0.7742; Speed (i), F(2,21) = 0.1366, p = 0.8731. l, m The passive avoidance test: the latency to enter the dark chamber at the preshock, and 24 h, 72 h, and 120 h after shock (l), and the freezing time 24 h after shock (m) for the indicated groups. n = 7 (WT), 8 (Tg), and 10 (Tg+Lpc-EV). Preshock, F(2,24) = 0.7906, p = 0.4650; 24 h, F(2,24) = 9.480, p = 0.0009; 72 h, F(2,24) = 10.23, p = 0.0006; 120 h, F(2,24) = 6.479, p = 0.0056; freezing time, F(2,24) = 7.227, p = 0.0035. Data are presented as the mean ± SEM. *p < 0.05; **p < 0.01, difference between indicated groups; #p < 0.05; ##p < 0.01, difference between Tg and Tg-Lpc-EV (Student’s t-test; one-way ANOVA followed by the Newman‒Keuls post hoc test; and two-way repeated-measures ANOVA followed by the Bonferroni post hoc test).