Figure 8.

Preventive treatment with AZD8055 and PF4708671 does not improve the epileptic phenotype despite reduced levels of pS6^Ser240/244. (A) Seizure onset graph of Tsc1‐Cre⁺ mice treated with vehicle, AZD8055 (15 mg/kg), or PF4708671 (75 mg/kg) started 4 days after initiation of gene deletion. (B) Survival curves of the Tsc1‐Cre⁺ mice treated with AZD8055 and PF4708671. (C and D) Average seizure frequency is not different between the treated mice and control mice. Each line represents the average number of seizures per mouse with the squares indicating the day of onset and the triangles the day of death. (E and F) Western blot of cortical and hippocampal tissue of an independent group of mice treated with AZD8055 sacrificed on day 12, 2 h after the last drug injection. Levels of pS6^Ser240/244 are significantly lower in the cortex and hippocampus of the AZD8055‐treated mice. Although statistically not different, lower levels of pAkt are observed in AZD8055‐treated mice. (G) Mice treated with PF4708671 show significant lower pS6^Ser240/244 levels in the hippocampus. Seizure onset and survival were analyzed with a Kapler–Meier Log Rank test. Average frequency was compared with a one‐way ANOVA and Dunnett’s post hoc test. Western blot data is presented as means with error bars representing SEM. Sample sizes are indicated in the figures with n the number of mice used. Blots shown are representative but in some cases the order of the samples was adjusted to allow alignment with the corresponding bar. A one‐way ANOVA was used for statistical analysis with a Dunnett’s test as post hoc test. Tsc1‐Cre + mice were used as control group. *P < 0.05, ***P < 0.001, ****P < 0.0001.