Fig. 6

NMZ-treated Aldh2^−/− mice show rescued learning, memory and CREB responsiveness in carbachol treated hippocampal slices. Reversal of the age-dependent decline in the spontaneous alternation rate and discrimination index in the Y-maze task (a) and NOR task (b), respectively, was observed in male and female Aldh2 ^−/− mice: after obtaining baseline measurements at 2.5–3 months, mice were randomized to drug or vehicle control groups (n = 8–11) and treated with NMZ (20/mg/kg/day p.o.) or vehicle at 3 months of age for a period of 12 weeks. Pre-randomization data were compared by an unpaired t-test and post-randomization groups by a one-way ANOVA with a Bonferroni post-hoc test. Hippocampal slices from 6 month old wild type and Aldh2 ^−/− mice that had been treated with NMZ or vehicle control for 12 weeks, were incubated with 50 μM carbachol or vehicle (Basal) for 30 mins and snap frozen. Immunoblot analysis for pCREB was performed using 30 μg protein of hippocampal homogenate, and immunoreactive bands were quantitated by densitometry (c). Data are presented as the mean ± S.D. (n = 3) and were analyzed by a one-way ANOVA with a Bonferroni post-hoc test: * significant differences from basal (** p < 0.01, ***p < 0.001); ψ significant difference compared to basal in all other groups (p < 0.05)