Fig. 4: Lpc-EV treatment restored the expression of neurotrophic factors and epigenetic factors 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 until sacrifice at 8 months. Arrow, time point for tissue preparation. b–d Expression levels of Bdnf, Nt3, Nt4/5, and TrkB (b); Mecp2, and Creb1 (c); Hdac2, Sirt1, Sirt5, Sirt7, Kdm4a, G9a, Setdb1, and Suv39h1 (d) in the hippocampus of wild-type control (WT), Tg-APP/PS1 mice (Tg), and Tg-APP/PS1 mice treated with Lpc-EV (Tg+ Lpc-EV). N = 6 per group. tBdnf, F(2,5) = 1.41, p = 0.0010; Nt3, F(2,15) = 0.6496, p = 0.5363; Nt4/5, F(2,15) = 8.35, p < 0.0001; TrkB, F(2,15) = 0.977, p = 0.0027; Mecp2, F(2,15) = 19.26, p < 0.0001; Creb1, F(2,15) = 4.858, p = 0.0236; Hdac2, F(2,15) = 6.694, p = 0.0084; Sirt1, F(2,21) = 10.73, p = 0.0006; Sirt5, F(2,15) = 7.347, p = 0.0060; Sirt7, F(2,15) = 5.725, p = 0.0142; Kdm4a, F(2,15) = 2.872, p = 0.0879; G9a, F(2,15) = 19.53, p < 0.0001; Setdb1, F(2,15) = 15.09, p = 0.0003; Suv39h1, F(2,15) = 59.31, p < 0.0001. e–i A diagram of the hippocampus and the regions examined (e). Photomicrographs showing MeCP2 (f) and Sirt1 (h) expression in CA1 and CA3 pyramidal neurons and DG neurons and their quantification levels (g, i) in wild-type control (WT), Tg-APP/PS1 mice (Tg-CON), and Tg-APP/PS1 mice treated with Lpc-EV (Tg+Lpc-EV). Scale bar, 100 μm. n = 7–11 animals. Mecp2; CA1, F(2,21) = 6.504, p = 0.0063; CA3, F(2,24) = 11.88, p = 0.0003; DG, F(2,24) = 11.83, p = 0.0003. n = 6–7 animals. Sirt1; CA1, F(2,16) = 4.694, p = 0.0249; CA3, F(2,16) = 4.605, p = 0.0263; DG, F(2,16) = 3.377, p = 0.0598. Data are presented as the mean ± SEM. *p < 0.05; **p < 0.01 (one-way ANOVA followed by the Newman‒Keuls post hoc test).