Journal: Molecular Psychiatry
Article Title: C/EBPβ is a key transcription factor for APOE and preferentially mediates ApoE4 expression in Alzheimer’s disease
doi: 10.1038/s41380-020-00956-4
Figure Lengend Snippet: Viral injection of ApoE3 or ApoE4 into C/EBPβ+/+; C/EBPβ+/−; 3xTg and 3xTg/C/EBPβ+/− mice (3 months old) for 3 months. A The hippocampal tissues were analyzed by immunoblotting (n = 2 mice per group, arrow: full-length AEP, arrowhead: activated AEP). B, C Overexpression of ApoE4 increased the activity of AEP and expression of Aβ. Each mouse is analyzed three times and the averaged values are plotted and subjected to statistical analyses (n = 3 mice/group, mean ± SEM, **P < 0.01, two-way ANOVA and Bonferroni’s post hoc test). D ApoE4 overexpression enhanced the early formation of amyloid plaques in wild-type or 3xTg mice, and downregulation of C/EBPβ decreased Aβ aggregates, co-staining with Aβ and THS, Scale bar: 100 μm. E Quantification from both 4G8 and THS-positive signals, n = 5, 2 mice/group, 2–3 slices/mouse (mean ± SEM, *P < 0.05, **P < 0.01 vs. group 1, two-way ANOVA and Bonferroni’s post hoc test). F, G Electrophysiology analysis. ApoE4 overexpression worsened the LTP defects in wild-type or 3xTg mice. LTP of fEPSPs (mean ± SEM; n = 6 in each group; *P < 0.05, **P < 0.01 compared with group1, two-way ANOVA and Bonferroni’s post hoc test). Shown traces were representative fEPSPs of ten samples recorded before and after TBS (theta-burst stimulation). H Quantification of fEPSP potentiation from the final 10 min of recordings (86–95 min in Fig. 4G, H) normalized to basal levels. Representative recording traces: black line, baseline; red line, LTP 86–95 min (mean ± SEM; n = 6 in each group; *P < 0.05 compared with 3xTg-control, two-way ANOVA and Bonferroni’s post hoc test). I, J Morris water maze analysis. ApoE4 overexpression exacerbated the learning and memory dysfunctions (mean ± SEM; n = 7–8 mice per group; *P < 0.05 compared with group1, two-way ANOVA and Bonferroni’s post hoc test). K, L Fear condition tests. Contextual and cued fear conditions were reduced in ApoE overexpressed mice. (Mean ± SEM; n = 7–8 mice per group; *P < 0.05, **P < 0.01 compared with group1, two-way ANOVA and Bonferroni’s post hoc test). See also Supplementary Fig. 11.
Article Snippet: Differentiation of human iPSC-derived NSCs into neurons The used human induced pluripotent stem cell (iPSC)-derived NSCs were obtained from two donors: ax0111 from AD patient with ApoE4/4 genotype, ax0112 from AD patient with ApoE3/3 genotype (Axol Bioscience, Cambridge, UK).
Techniques: Injection, Western Blot, Over Expression, Activity Assay, Expressing, Staining