Fig. 4. Pharmacological inhibition of the BDNF-TrkB signaling pathway induces depression and anxiety-like behaviors in neuron-specific Pdcd4 knockout mice.
a Time course of tamoxifen/CRS administration and behavior tests. b Coronal sections of dentate gyrus (DG) from control or neuron-depleted mice stained for Pdcd4 after tamoxifen administration in iCre mice or ncKO mice scale bars, 50 µm. c Quantitative ELISA analysis of pan-BDNF protein expression in the hippocampus in No-CRS and CRS at iCre mice or ncKO mice. n = 5–6 per group; mean ± SEM, two-way ANOVA (iCre vs. ncKO, F1,18 = 10.09, P < 0.01; No-CRS vs. CRS, F1,18 = 2.048, P = 0.1696; interaction, F1,18 = 5.433, P < 0.05) and Sidak’s multiple comparison test, *P < 0.05, **P < 0.01. d Representative photomicrographs of dendritic spines from DG neurons, Scale bar, 10 μm. e Spine density in dendrites of DG neurons in Pdcd4 cKO and Cre mice. n = 4 per group; mean ± SEM, two-way ANOVA, *P < 0.05, **P < 0.01 vs. the No-CRS group; #P < 0.05, ##P < 0.01 vs. the CRS-cKO group. f Immobility time in TST, mean ± SEM, two-way ANOVA (iCre vs. ncKO, F1,45 = 0.2672, P = 0.6078; No-CRS vs. CRS, F1,45 = 0.1892, P = 0.6656; interaction, F1,45 = 8.49, P < 0.01) and Sidak’s multiple comparison test, *P < 0.05, **P < 0.01. Under stress condition, one-way ANOVA (F3,40 = 3.931, P < 0.01) and Tukey’s multiple comparison test, *P < 0.05, **P < 0.01. g Immobility time in FST, mean ± SEM, two-way ANOVA (iCre vs. ncKO, F1,45 = 2.533, P = 0.1185; No-CRS vs. CRS, F1,45 = 5.604, P < 0.05; interaction, F1,45 = 16.13, P < 0.01) and Sidak’s multiple comparison test, *P < 0.05, **P < 0.01. Under stress condition, one-way ANOVA (F3,40 = 6.553, P < 0.01) and Tukey’s multiple comparison test, *P < 0.05, **P < 0.01. h Sucrose consumption in SPT. Mean ± SEM, two-way ANOVA (iCre vs. ncKO, F1,45 = 5.085, P < 0.05; No-CRS vs. CRS, F1,45 = 17.32, P < 0.01; interaction, F1,45 = 20.25, P < 0.01) and Sidak’s multiple comparison test, *P < 0.05, **P < 0.01. Under stress condition, one-way ANOVA (F3,40 = 9.42, P < 0.01) and Tukey’s multiple comparison test, *P < 0.05, **P < 0.01. i, j Locomotion and time spent in center in the open field test. Mean ± SEM, two-way ANOVA (iCre vs. ncKO, F1,45 = 0.6502, P = 0.4244; No-CRS vs. CRS, F1,45 = 17.32, P < 0.01; interaction, F1,45 = 14.23, P < 0.01) and Sidak’s multiple comparison test, *P < 0.05, **P < 0.01. Under stress condition, one-way ANOVA (F3,40 = 17.29, P < 0.01) and Tukey’s multiple comparison test, *P < 0.05, **P < 0.01. k Time spent in open arm in the elevated plus maze. Mean ± SEM, two-way ANOVA (iCre vs. ncKO, F1,45 = 1.914, P = 0.1734; No-CRS vs. CRS, F1,45 = 2.057, P = 0.1584; interaction, F1,45 = 11.3, P < 0.01) and Sidak’s multiple comparison test, *P < 0.05, **P < 0.01. Under stress condition, one-way ANOVA (F3,40 = 9.218, P < 0.01) and Tukey’s multiple comparison test, *P < 0.05, **P < 0.01.