Fig. 4

CPE-upregulating miRNA agomirs promote hippocampal neurogenesis, newborn-neuron dendrite development and mBDNF generation in APP/PS1 mice. a Representative images and quantification of BrdU and DCX double-labelled newly generated neurons in the DG of 9-MO WT and APP/PS1 mice. Scale bar, 100 µm. Data are presented as mean ± SEM, n = four mice each group. Two-tailed Student’s t test. b Representative images of proBDNF, mBDNF, TrkB and CPE expression in the DG of 9-MO female APP/PS1 transgenic mice compared with age-matched WT mice. Scale bars, 20 µm. Dashed line indicates the SGZ. Arrowheads indicate SOX2⁺CPE⁺ cells in the SGZ. c The timeline of the experiments for immunofluorescence and behavioral tests after intracerebreventricular (icv) injection or intranasal instillation of miRNA agomirs in APP/PS1 mice. d Hippocampi images of PBS or CY3-labeled NC-agomir (red) intranasally  delivered in 9-MO APP/PS1 mice. e Quantification of SOX2⁺CPE⁺ cells in the SGZ of 9-MO APP/PS1 mice 2 weeks after icv injection or on day 21 of intranasal instillation of miRNA agomirs. f Representative images and normalized fluorescence intensity of mBDNF and PSA-NCAM expression in the DG of 9-MO APP/PS1 mice treated with miRNA agomirs 2 weeks after icv injection or on day 21 of intranasal instillation. Scale bars, 20 µm. g Quantification of BrdU⁺ and BrdU⁺DCX⁺ cells in the DG of 9-MO APP/PS1 mice treated with miRNA agomirs 2 weeks after icv injection or on day 21 of intranasal instillation. h Representative images (Left) and sample traces (Right) of the morphology of DCX-positive immature neurons in the DG of 9-MO APP/PS1 mice 3 weeks following icv or intranasal delivery of agomirs. Scale bars, 20 µm. i, j Quantification of the total dendritic length (i) and dendritic complexity (j) of DCX-positive immature neurons in (h). n = 20–35 neurons from three mice each group. Data are presented as mean ± SEM. One-way ANOVA. For (e), (f) and (g), data are presented as mean ± SEM, n = three mice each group. Data were analyzed with one-way ANOVA