Fig. 7
Effect of ganaxolone on Shank3 KO mice. A Quantification of the number of PV neurons in the hippocampus. Shank3 KO mice did not present alteration in the number of Parvalbumin interneurons. Data from the CA1 were analyzed by one-way ANOVA; quantification of the CA3 and DG was analyzed by Kruskal–Wallis test; n = 17 Pv-Cre+/− Shank3Wt/Wt, n = 16 Pv-Cre+/− Shank3Fl/Wt, n = 16 Shank3 KO; ** p < 0.01; *** p < 0.001; n = number of bilateral slides analyzed; 3 animals used for each group; CA1 = Cornu Ammonis-1; CA3 = Cornu Ammonis-3; DG = dentate gyrus. B Quantification of the number of PV neurons in the medial prefrontal cortex were analyzed by one-way ANOVA; n = 10 Pv-Cre+/− Shank3Wt/Wt, n = 10 Pv-Cre+/− Shank3Fl/Wt, n = 10 Shank3 KO; n = number of bilateral slides analyzed; 3 animals used for each group. C Quantification of the number of PV neurons in the visual cortex were analyzed by one-way ANOVA; n = 8 Pv-Cre ± Shank3Wt/Wt, n = 11 Pv-Cre ± Shank3Fl/Wt, n = 8 Shank3 KO. n = number of bilateral slides analyzed. D Representative western blots and relative protein quantification from hippocampal PSD-enriched fraction derived from adult mice. Data obtained from the quantification of Shank3 were analyzed by Brown-Forsythe and Welch ANOVA; GABA-A-R-alpha1 was analyzed by Kruskal–Wallis test. Shank3 n = 6 for each group; GABA-A-R-alpha1 n = 11 Pv-Cre+/− Shank3Wt/Wt and Pv-Cre+/− Shank3Fl/Wt, n = 10 Shank3 WT, n = 9 Shank3 KO. * p < 0.05; ** p < 0.01; *** p < 0.001. E Representative western blots and relative protein quantification from cortical PSD-enriched fraction derived from adult mice. Data obtained from the quantification of Shank3 was analyzed by Brown-Forsythe and Welch ANOVA. GABA-A-R-alpha1 protein quantification was analyzed by Kruskal–Wallis test. Shank3 n = 12 for each group; GABA-A-R-alpha1 n = 13 for each group. * p < 0.05; **** p < 0.0001. F Evaluation of evocative memory in Wt and Shank3 KO mice after ganaxolone treatment was evaluated by calculating a discrimination index in the novel object recognition test. Data were analyzed by two-way ANOVA; n = 8 Wt vehicle, n = 8 Wt ganaxolone, n = 8 Shank3 KO vehicle, n = 9 Shank3 KO ganaxolone; * p < 0.5; *** p < 0.001 Wt vehicle compared with Shank3 KO vehicle; $ p < 0.05; $$$ p < 0.001 Shank3 KO vehicle compared with Shank3 KO ganaxolone. G Repetitive grooming behavior was analyzed by two-way ANOVA; n = 8 Wt vehicle, n = 6 Wt ganaxolone, n = 7 Shank3 KO vehicle, n = 8 Shank3 KO ganaxolone; ** p < 0.01 Shank3 Wt vehicle compared with Shank3 KO vehicle; $ p < 0.05 Shank3 KO vehicle compared with Shank3 KO ganaxolone