Fig. 7

Pharmacological inhibition of eEF2K activity rescues the epileptic phenotype in Scn1a ± mice and improve autistic-like behavior and memory impairment.A Experimental timeline. B Representative western blots and relative quantification show a significantly reduction of phosphorylated eEF2 and no differences in eEF2 expression levels in total homogenate of hippocampus (left) and cerebral cortex (right) of Scn1a ± mice after a chronic treatment of 10 days with 1 mg/day dose of A484954 compared with placebo. All data are presented as mean ± SEM. N = 5 per group. Statistical analysis **p < 0.01 versus corresponding Scn1a ± treated with placebo; Unpaired two-tailed t-test. C Representative EEG traces (a 60 min registration is shown) in basal condition and at 9 days of treatment of a Scn1a ± mouse treated with placebo or A484954. D Quantification of the number of EEG spikes calculated in percentage per 24 h in basal condition and at 3, 6 and 9 days of treatment. Significant reduction of the number of EEG spikes across the three EEG recording in Scn1a ± mice treated with A484954. No difference in number of EEG spikes in Scn1a ± mice treated with placebo. Scn1a ± mice treated with A484954 n = 5, Scn1a ± mice treated with placebo n = 5. Statistical analysis **p < 0.01 versus corresponding EEG basal, $p < 0.05 versus corresponding EEG at 3 days of treatment; Friedman test. E Significant reduction in repetitive grooming behavior in Scn1a ± mice before and after treatment with A484954 and in Scn1a ± mice treated with A484954 compared with Scn1a ± mice treated with placebo. Repetitive grooming is evaluated as time spent in self-grooming over 10 min observations. Data are presented as mean ± SEM. N = 5 per group. Statistical analysis **p < 0.01 versus corresponding Scn1a ± mice before treatment with A484954; $$p < 0.01 versus corresponding Scn1a ± mice after treatment with placebo; Two-way ANOVA. F Discrimination index evaluated in the novel object recognition test at the end of treatment shows a memory improvement in Scn1a ± mice treated with A484954 compared with animals treated with placebo at 120 min and 24 h after familiarization phase. Data are presented as mean ± SEM. N = 5 per group. Statistical analysis *p < 0.05, **p < 0.01 versus corresponding Scn1a ± mice treated with placebo. Unpaired two-tailed t-test for 5 min and 120 min; Two-tailed Mann–Whitney test for 24 h