Fig. 1

CPE and the BDNF–TrkB signaling in the hippocampus are downregulated during aging. a The CPE protein expression in the DG of 2-MO WT mice. Ho, Hoechst. Scale bars, 20 μm. b Characterization of CPE-positive NSCs in the SGZ of 2-MO WT mice. White arrowheads indicate SOX2⁺CPE⁺GFAP⁺ NSCs (top panels), CPE⁺HMGB2⁺ intermediate progenitor cells (IPCs, middle panels) and CPE⁺DCX⁺ neuroblasts (NBs, bottom panels) in the SGZ. Scale bars, 10 µm. c In situ hybridization analysis of CPE mRNA in the hippocampus of WT mice at 2, 8, 12 and 18 MO. Scale bar, 100 µm. GCL, granular cell layer; SGZ, subgranular zone; ML, molecular layer. d Representative images and normalized fluorescence intensity of CPE expression in the SGZ of WT mice at 2, 8, 12 and 18 MO. Scale bar, 20 µm. White arrowheads indicate SOX2⁺CPE⁺ cells in the SGZ. e Western blotting analyses of proteins extracted from the mixed tissues of the hippocampus from three WT mice at each age. Relative quantification of CPE levels in the DG is shown on the right. f Representative images of SGZ immunostaining for CPE, mBDNF and TrkB of 2-MO WT mice. Scale bar, 10 μm. White arrowheads indicate TrkB⁺CPE⁺mBDNF⁺ cells. g Representative images and normalized fluorescence intensity of proBDNF/mBDNF, TrkB and p-TrkB expression in the DG of WT mice at 2, 8, 12 and 18 MO. Scale bars, 10 µm. Dashed lines indicate the SGZ. h Western blotting analyses of proteins extracted from the mixed tissues of the hippocampus from three WT mice at each age (upper panel). Relative quantification of each protein level in the DG is shown in the lower panel. For (d), (e), (g) and (h), data are presented as mean ± SEM. n = three/four mice each age. Data were analyzed with one-way ANOVA