FIGURE 4.

CAST overexpression blocks Tau phosphorylation and promotes spatial learning of APP/PS1 mice. A–F, hippocampal homogenates (∼50 μg of protein) from 12-month-old female littermate mice were subjected to IB with indicated antibodies. Shown are representative blots against phosphorylated Tau (AT8) or total Tau (Tau-5) (A), phosphorylated CREB (p-CREB) or total CREB (C), and phosphorylated ERK (p-ERK) or total ERK (E), respectively. The values for AT8/Tau-5 (B), p-CREB/CREB (D), or p-ERK/ERK (F) were quantified with values from WT mice set as 1.0. Shown are the means ± S.E. (n = 6 animals of each group in B, n = 5 in D, and n = 6 in F). G–L, overexpression of hCAST in APP/PS1 mice prevents learning and memory deficits in the Morris water maze. Mice at different ages were analyzed (G–I, ∼7-month-old female mice; J–L, ∼15-month-old male mice) for escape latency (G and J) after training for different days. After training for 5 days, a probe test was given to determine the percentage of time spent in the target quadrant (H and K) or number of target crossings (I and L) within 60 s. The number of animals in each group is indicated in the histograms (G and J). *, p < 0.05; **, p < 0.01; ***, p < 0.001, ANOVA with Student's t test.