Fig. 8: Loss of REST accelerates neurodegeneration and cognitive decline in AD mice.
From: A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer’s disease
a, b Increased neurodegeneration in REST-deficient 3xTg mice. a TUNEL labeling (green), immunolabeling for p-Ser202 tau (pTau) (antibody CP13, red), and DAPI labeling for DNA identifies TUNEL-positive nuclei in neurons with NFT-like tau pathology in hippocampal CA1 (top 2 panels) and CA3 (lower 2 panels) sectors in 29-month-old 3xTg;GT but not 3xTg mice. b Quantification of TUNEL-positive cells in 27–29-month-old WT (n = 4), GT (n = 3), 3xTg (n = 6) and 3xTg;GT (n = 6) mice. P-values were generated by two-way ANOVA with Tukey’s post-hoc test. Scale bar, 25 μm. c Time course of spatial learning in the Morris water maze for 17–18-month-old mice of the indicated genotypes. d Memory retrieval in the probe trial of the Morris water maze. Shown are the numbers of entries in the target (platform) area and time spent in target (platform) area for 17–18-month-old mice of the indicated genotypes. Two-way ANOVA revealed no significant interaction between REST genotype (+/+, cHET) and AD pathology (WT, 3xTg): F (1, 51) = 2.41, P = 0.12. One-way ANOVA with Tukey’s post-hoc test was then conducted and the P-values are shown. Panels c, d: n = 17 WT, n = 11 REST cHET, n = 16 3xTg, and n = 11 3xTg;cHET mice. e Time course of spatial learning in the Morris water maze for 12–14-month-old mice of the indicated genotypes. REST loss-of-function alleles do not further impair learning in J-20 mice. f Memory retrieval in the probe trial for 12–14-month-old mice of the indicated genotypes. J-20 mice have impaired memory retrieval relative to WT mice by two-tailed Mann–Whitney U test. Two-way ANOVA revealed no significant interaction between REST genotype (+/+, cHET, cKO) and AD pathology (WT, J20): F (2,100) = 0.82, P = 0.44. Kruskal–Wallis one-way ANOVA with Dunn’s post-hoc test was then conducted and the P-values are shown. Panels e, f: n = 17 WT, n = 14 REST cHET, n = 18 REST cKO, n = 31 J20, n = 8 J20;cHET and n = 18 J20;cKO mice. b, d, f Shown are individual values and the mean ± S.E.M. c, e Shown are the mean ± S.E.M, and P-values for planned comparisons by the two-tailed unpaired t-test. Source data are provided as a Source Data file.
