S100B and APP Promote a Gliocentric Shift and Impaired Neurogenesis in Down Syndrome Neural Progenitors (original) (raw)
Figure 4
Gliocentric shift due to S100B and APP/Aβ42 in DS HNPs.
(A) Lentiviral infections of ZsGreen-APP or transfections of EGFP-S100B constructs into normal HNPs for 4 days promote GFAP and inhibit MAP2 expression, as shown by western blot. (B) Pretreatment of normal, cultured HNPs with increasing concentrations of soluble S100B or Aβ42 for 24 hours shows a dose-dependent increase in GFAP and decrease in MAP2 expression. Co-treatment with S100B and Aβ42 for 24 hours leads to an additive increase in GFAP and decrease in MAP2 expression levels. (C) Quantification graphs from fluorescent photomicrographs (Figure S4A) in the cortex of early postnatal (P0) Ts65Dn mice show increased numbers of immunostaining on glial markers such as S100B, GFAP and PDGFRA, and decreased numbers of neuronal staining with MAP2 compared to WT (n = 3 for each group of mice). A similar increase appears in APP (Tg2576) or APP/S100B (Tg2576-huS100B) overexpressing mice compared to age-matched WT control (Figure S4B and S4C). Data are represented as mean +/− STDEV, * p-value<0.05, ** p-value<0.01, *** p-value<0.001 by two tailed t-test and one-way ANOVA.