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Fig. 6 | Molecular Autism

Fig. 6

From: Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K)

Fig. 6

eEF2K deletion in Scn1a ± mice rescues the learning and memory impairment and social recognition alteration. A, B Discrimination index evaluated in the novel object recognition test (A) and in the spatial object recognition test (B). A Scn1a ± mice show an impairment in novel object recognition at 5 min, 120 min and 24 h after the familiarization phase compared with WT and Scn1a ± eEF2K−/− mice. Data are presented as mean ± SEM. 5 min and 24 h: WT n = 15, Scn1a ± n = 14, Scn1a ± eEF2K−/− n = 11; 120 min WT n = 15 Scn1a ± n = 14, Scn1a ± eEF2K−/− = 10. Statistical analysis *p < 0.05, ***p < 0.001 versus corresponding WT, $p < 0.05, $$p < 0.01, $$$p < 0.001 versus corresponding Scn1a ± ; Kruskal–Wallis test, Dunn’s post hoc. B Scn1a ± mice are impaired in spatial object recognition test at 5 min, 120 min and 24 h after familiarization phase when compared with WT and Scn1a ± eEF2K−/− mice. Data are presented as mean ± SEM. WT n = 11, Scn1a ± n = 13, Scn1a ± eEF2K−/− n = 13. Statistical analysis **p < 0.01, ***p < 0.001 versus corresponding WT, $p < 0.05, $$$p < 0.001 versus corresponding Scn1a ± ; Kruskal–Wallis test, Dunn’s post hoc for 5 min and One-way ANOVA, Tukey’s post hoc for 120 min and 24 h. C Scn1a ± mice required more days to achieve the criterion than WT mice during the reversal phase of T-maze. Data are presented as mean ± SEM. N = 10 per group. Statistical analysis *p < 0.05 versus corresponding WT. Days to reach the criterion was analyzed by One-way ANOVA, Tukey’s post hoc. The percentage of animals reaching the criterion was analyzed by Fisher's exact test. D, E Acquisition and reversal learning in Morris water maze task in terms of latency to reach the platform across 4 days trial and probe test and in percentage of the time spent in the target quadrant during the probe test. D Scn1a ± mice display normal Morris water maze learning in the acquisition phase in both latency to reach the platform and in probe test. Data are presented as mean ± SEM. WT, Scn1a ± n = 10, Scn1a ± eEF2K−/− n = 9. Each day latency was analyzed by Kruskal–Wallis test, Dunn’s post hoc and the acquisition probe test latency was analyzed by One-way ANOVA, Tukey’s post hoc. AUC and percentage in the target zone were analyzed by One-way ANOVA, Tukey’s post hoc. E Scn1a ± mice show an impaired spatial memory in Morris water maze probe test in the reversal phase. Data are presented as mean ± SEM. WT, Scn1a ± n = 10, Scn1a ± eEF2K−/− n = 9. Each day of latency was analyzed by Kruskal–Wallis test, Dunn’s post hoc. Statistical analysis in reversal probe test latency **p < 0.01 versus corresponding WT; One-way ANOVA, Tukey’s post hoc. AUC was analyzed by Kruskal–Wallis test, Dunn’s post hoc. Statistical analysis for percentage of time in the target zone *p < 0.05 versus corresponding WT; One-way ANOVA, Tukey’s post hoc. F Sociability index (left) and social novelty preference index (right) evaluated in sociability (left) and in social novelty test (right). Scn1a ± mice display a normal social attitude when compared with WT and Scn1a ± eEF2K−/− mice in sociability test (left). Data are presented as mean ± SEM. WT, Scn1a ± n = 9, Scn1a ± eEF2K−/− n = 8; One-way ANOVA, Tukey’s post hoc. Scn1a ± display an impairment in social recognition when tested for social novelty test (right). Data are presented as mean ± SEM. WT n = 9, Scn1a ± n = 10, Scn1a ± eEF2K−/− n = 8. Statistical analysis *p < 0.05 versus corresponding WT; One-way ANOVA, Tukey’s post hoc

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