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. 2020 Mar 20;10:101. doi: 10.1038/s41398-020-0782-1

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a–c The expression of HCN1 (one-way ANOVA: F(2, 9) = 46.185, p = 0.000; Post-hoc test: SPS&S + ZD7288: p = 0.001, SPS&S + 8-Br-cAMP: p = 0.003), BDNF (one-way ANOVA: F(2, 9) = 10.446, p = 0.005; Post-hoc test: SPS&S + ZD7288: p = 0.005, SPS&S + 8-Br-cAMP: p = 0.885) and pmTOR (one-way ANOVA: F(2, 9) = 23.233, p = 0.000; Post-hoc test: SPS&S + ZD7288: p = 0.002, SPS&S + 8-Br-cAMP: p = 0.135) in PFC. g–i The expression of HCN1 (one-way ANOVA: F(2, 9) = 91.914, p = 0.000; Post-hoc test: SPS&S + ZD7288: p = 0.000, SPS&S + 8-Br-cAMP: p = 0.000), BDNF(one-way ANOVA: F(2, 9) = 26.364, p = 0.000; Post-hoc test: SPS&S + ZD7288: p = 0.039, SPS&S + 8-Br-cAMP: p = 0.003) and pmTOR(one-way ANOVA: F(2, 9) = 24.342, p = 0.000; Post-hoc test: SPS&S + ZD7288: p = 0.000, SPS&S + 8-Br-cAMP: p = 0.063) in Hip. d–f, j–l Localization and distribution of HCN1, BDNF and pmTOR in PFC (d–f) and (j–l). Bar = 20 μm. m, n The correlation between the level of BDNF and pmTOR in the PFC (m) and Hip (n) analyzed with linear regression. Data are represented as mean ± SEM. *p < 0.05 was expressed statistically significant. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with SPS&S + Vehicle group. The mediator effect test of BDNF (bootstrap) with a sample size of 5000 and 95% confidence interval showed that the BDNF was a mediator between HCN1 and pmTOR in the PFC (model: X_pmTOR = 0.0104×_HCN1 + 0.9152×_BDNF, confidence interval: [−0.7259, −0.0211], effect: −0.3802) and Hip (model: X_pmTOR = 0.7760×_HCN1 + 0.7211×_BDNF, confidence interval: [0.4280,1.1241], effect: 0.3186).