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. 2017 Apr 28;7:1256. doi: 10.1038/s41598-017-01218-0

Figure 8.

Figure 8

Inhibition of MEK with PD0325901 restores pERK levels but does not rescue the spatial learning deficit. (A) Western blots of hippocampal lysates of WT and HRas G12V/G12V mice treated with vehicle, 2 and 5 mg/kg of PD0325901. (B) Quantification of Western blots showing that both doses used affect pERK levels in both wild-type and HRas G12V/G12V mice. For both 2 and 5 mg/kg: effect of genotype: P < 0.01, effect of treatment: P < 0.01, interaction genotype*treatment P < 0.01. Data are presented as mean ± SEM from 6 mice per group. Two mice per group are depicted in the example blot. Statistical test: two-way ANOVA. (C) Average latency to platform for each day of training, per genotype. On average longer latencies were observed in vehicle and PD0325901 drug treated HRas G12V/G12V mice (effect of genotype P < 0.01). (D) Spatial memory assessed in a probe trial reveals a significant effect of genotype (P < 0.05) on time spent in the target quadrant (TQ). Although PD0325901 significantly reduced performance of wild-type mice, it showed no effect on mutant mice and no interaction of genotype and treatment was observed (P = 0.28). TQ = target quadrant, RQ = adjacent right quadrant, LQ = adjacent left quadrant, OQ = opposite quadrant. Heat plots present the data of all tracks combined, in which the color indicates the mean time spent at that position in the pool. Data are presented as mean ± SEM from: vehicle group: wild-type n = 14 mice; HRas G12V/G12V n = 14 mice; treated group: wild-type n = 13 mice; HRas G12V/G12V n = 13 mice. Statistical test: repeated measures two-way ANOVA and two-way MANOVA, respectively. (E) Western blot of hippocampal tissue taken from WT and HRas G12V/G12V mice after water maze training and concurrent treatment with either vehicle or PD0325901. (F) Quantification of Western blots. A significant effect of genotype (F 1,37 = 47.83 P < 0.01) and treatment (P < 0.01) on pERK was observed. No interaction effect of genotype and treatment was found (P = 0.37). Data are presented as mean ± SEM from n = 10 mice per group. Statistical test: unpaired two-tailed t-test.