Fig. 1.

Age-dependent modulation of cell proliferation, cell differentiation, and neurogenesis in S7ΔEx1 mutant mice.

(A) Numbers of PCNA⁺ cells within the DG (A′) and SVZ (A″) are significantly increased in 4 month-old S7ΔEx1 mice compared to age-matched WT. In contrast, in 12 month-old animals, numbers of PCNA⁺ cells are significantly lower in transgenic compared to WT animals. (B) Numbers of DCX⁺ cells do not differ between the 4 month old S7ΔEx1 and WT mice in the DG (B′) and the SVZ (B″). At 12 months, S7ΔEx1 mice show a significant reduction of DCX⁺ cells. (C) In the DG of 4 month-old S7ΔEx1 mice, Nestin and Sox2 cell numbers are significantly elevated compared to WT (C′), and Sox2 cell numbers are significantly higher in the SVZ in the young transgenic mice (C″). At 12 months, the numbers of Nestin⁺ and Sox2⁺ cells are similar in WT and knockout mice in the DG and the SVZ. (D) PCNA expression within the Nestin⁺ cell population is decreased in 12 month-old S7ΔEx1 mice compared to WT mice (p = 0.075). In contrast, the proliferative activity (PCNA⁺) of DCX⁺ neuronal progenitor cells does not differ between 12 month-old WT and S7ΔEx1 mice. (E) Numbers of BrdU positive cells in the DG (E′) and SVZ (E″) were significantly higher in the young transgenic compared to WT mice, but did not differ in the 12 month-old mice. In the DG, the survival index of newly generated cells, based on BrdU cell number divided by PCNA cell number, was significantly higher in the 12 month-old S7ΔEx1 animals compared to the WT mice (E‴). (F) Cell fate analyses by BrdU co-labeling with specific markers revealed no differences in the percentage of BrdU double labeled cells in the DG (F′) and the SVZ (F″) between old transgenic and WT mice. In young mice, the fraction of BrdU⁺/NeuN⁺ cells was significantly lower in the S7ΔEx1 mice. In addition, independent of their genotype, young mice possessed a significant higher percentage of BrdU⁺/Sox2⁺ cells in the SVZ than aged mice (F″) Scale bars: 100 μm.