Fig. 3: Lpc-EV counteracted the Aβ42-induced downregulation of neurotrophic factors via the upregulation of epigenetic factors in HT22 cells. | Experimental & Molecular Medicine

Fig. 3: Lpc-EV counteracted the Aβ42-induced downregulation of neurotrophic factors via the upregulation of epigenetic factors in HT22 cells.

From: Lactobacillus-derived extracellular vesicles counteract Aβ42-induced abnormal transcriptional changes through the upregulation of MeCP2 and Sirt1 and improve Aβ pathology in Tg-APP/PS1 mice

Fig. 3

a–d Expression levels of Bdnf, Nt3, Nt4/5, and TrkB in HT22 cells treated with Aβ42 (1 μM), Aβ42 plus Lpc-EV (10 μg/ml), or Aβ42 plus Lpc-EV and the indicated siRNA: siRNA-Mecp2 (a), siRNA-Sirt1 (b), siRNA-Sirt5 (c), and siRNA-Kdm4a (d). siRNA-control, siCON. n = 8 per group. siRNA-Mecp2 (a), t(14) = 19.57, p < 0.0001; tBdnf, F(3,28) = 6.796, p = 0.0063; Nt3, F(3,28) = 7.576, p = 0.0042; Nt4/5, F(3,28) = 8.263, p = 0.0030; TrkB, F(3,28) = 12.02, p = 0.0006. siRNA-Sirt1 (b), t(14) = 10.80, p < 0.0001; tBdnf, F(3,28) = 11.67, p = 0.0007; Nt3, F(3,28) = 12.06, p = 0.0006; Nt4/5, F(3,28) = 11.13, p = 0.0009; TrkB, F(3,28) = 7.572, p = 0.0042. siRNA-Sirt5 (c), t(14) = 13.15, p < 0.0001; tBdnf, F(3,28) = 34.05, p < 0.0001; Nt3, F(3,28) = 30.44, p < 0.0001; Nt4/5, F(3,28) = 12.35, p = 0.0002; TrkB, F(3,28) = 56.56, p < 0.0001. siRNA-Kdm4a (d), t(14) = 19.51, p < 0.0001; tBdnf, F(3,28) = 35.21, p < 0.0001; Nt3, F(3,28) = 15.21, p = 0.0002; Nt4/5, F(3,28) = 16.18, p = 0.0002; TrkB, F(3,28) = 26.28, p < 0.0001. e–l Expression of Hdac2, Sirt1, Sirt5, Setdb1, Kdm4a, G9a, Mecp2, and Creb1 in HT22 cells treated with Aβ42 (1 μM), Aβ42 plus Lpc-EV (10 μg/ml), or Aβ42 and Lpc-EV plus the indicated siRNA: siRNA-MeCP2 (e, f), siRNA-Sirt1 (g, h), siRNA-Sirt5 (i, j), and siRNA-Kdm4a (k, l). n = 8 per group. siRNA-MeCP2 (e, f); Hdac2, F(3, 28) = 15.57, p = 0.0002; Sirt1, F(3,28) = 8.921, p = 0.0022; Sirt5, F(3,28) = 42.61, p < 0.0001; Kdm4a, F(3,28) = 5.852, p = 0.0106; G9a, F(3,28) = 10.03, p = 0.0014; Setdb1, F(3,28) = 92.29, p < 0.0001; Creb1, F(3,28) = 251.8, p < 0.0001. siRNA-Sirt1 (g, h); Hdac2, F(3,28) = 8.184, p = 0.0031; Sirt5, F(3,28) = 8.068, p = 0.0033; Kdm4a, F(3,28) = 6.260, p = 0.0084; G9a, F(3,28) = 6.769, p = 0.0064; Setdb1, F(3,28) = 19.82, p < 0.0001; Mecp2, F(3,28) = 13.39, p = 0.0004; Creb1, F(3,28) = 8.748, p = 0.0024. siRNA-Sirt5 (i, j); Hdac2, F(3,28) = 10.66, p = 0.0011; Sirt1, F(3,28) = 6.476, p = 0.0074; Kdm4a, F(3,28) = 9.403, p = 0.0018; G9a, F(3,28) = 4.318, p = 0.0278; Setdb1, F(3,28) = 7.358, p = 0.0047; Mecp2, F(3,28) = 8.037, p = 0.0010; Creb1, F(3,28) = 17.04, p < 0.0001. siRNA-Kdm4a (k, l); Hdac2, F(3,28) = 14.64, p = 0.0003; Sirt1, F(3,28) = 42.24, p < 0.0001; Sirt5, F(3,28) = 19.79, p < 0.0001; G9a, F(3,28) = 14.07, p = 0.0003; Setdb1, F(3,28) = 18.06, p < 0.0001. Data are presented as the mean ± SEM. *p < 0.05; **p < 0.01 (Student’s t-test; and one-way ANOVA followed by the Newman‒Keuls post hoc test).

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