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. 2016 Nov 23;36(47):11946–11958. doi: 10.1523/JNEUROSCI.0672-16.2016

Figure 5.

Figure 5.

Chronic CTEP treatments of Mecp2 KO mice ameliorates hippocampal reduced soma size, prolongs lifespan, partially reduces long breath holdings, and ameliorates IA deficits. a, CTEP treatment ameliorates reduced neuronal soma size shown by averaged soma size by animals (WT_vehicle 100.17 ± 1.52 n = 7, WT_CTEP 101.51 ± 1.48 n = 4, KO_vehicle 91.99 ± 2.3 n = 7, KO_CTEP 99.11 ± 1.09 n = 7, 2-way ANOVA, interaction p = 0.123, drug treatment p = 0.028, genotype p = 0.008, Sidak's multiple-comparisons test WT_vehicle vs WT_CTEP n.s., KO_vehicle vs KO_CTEP *). b, CTEP treatment ameliorates reduced neuronal soma size in hippocampal CA1 neurons shown in cumulative distribution by cell numbers [KS test: WT_CTEP (n = 322 cells) vs WT_vehicle (n = 500 cells) p = 0.346, KO_vehicle vs WT_vehicle p = 0, KO_vehicle (n = 419 cells) vs KO_CTEP (n = 483 cells) p = 9.08 × 10−12, KO_CTEP vs WT_vehicle p = 0.042]. c, Kaplan–Meier survival curve showed that Mecp2 KO mice with treated CTEP survived longer than littermates treated with vehicle (KO_vehicle: n = 11 median survival is 83 d, KO_CTEP: n = 11, median survival is 113 d. Log-rank test, p = 0.038). d, Whole-body plethysmography analyses showed that CTEP treatment may partially reduce long breath holdings (>1 s) in Mecp2 KO mice (WT_vehicle 0.355 ± 0.118, n = 8; WT_CTEP 0.244 ± 0.056, n = 7; KO_vehicle 1.159 ± 0.218, n = 11; KO_CTEP 0.663 ± 0.129, n = 11; 2-way ANOVA, interaction p = 0.251, treatment p = 0.0748, genotype p = 0.0008, Tukey's multiple-comparisons test WT_vehicle vs KO_vehicle **, KO_vehicle vs WT_CTEP **, WT_CTEP vs KO_CTEP n.s., WT_vehicle vs KO_CTEP ns, WT_vehicle vs WT_CTEP n.s., KO_vehicle vs KO_CTEP n.s.). e, CTEP treatment ameliorated IA deficits in Mecp2 KO mice. CTEP treatment did not alter acquisition of IA in WT mice (WT_vehicle: 0 h 37.26 ± 8.26 n = 8, 24 h 217.36 ± 36.32 n = 8; 48 h 237.95 ± 71.17; WT_CTEP: 0 h 46.45 ± 7.92, 24 h 288.48 ± 47.71, 48 h 193.61 ± 46.36, n = 13, 2-way RM-ANOVA, interaction p = 0.286, treatment p = 0.794, time p < 0.0001; Sidak's multiple-comparisons test: 0 h vs 24 h **, 0 h vs 48 h **, 24 h vs 48 h ns, WT_vehicle n = 8; 0 h vs 24 h ****, 0 h vs 48 h **, 24 h vs 48 h n.s., WT_CTEP n = 13). CTEP treatment ameliorated acquisition deficits in Mecp2 KO mice (KO_vehicle: 0 h 28.59 ± 7.04, 24 h 86.6 ± 20.62, 48 h 52.21 ± 20.00 n = 8; KO_CTEP: 0 h 49.16 ± 10.73, 24 h 130.22 ± 16.80, 48 h 121.29 ± 28.81, n = 11; 2-way RM-ANOVA, interaction p = 0.383, treatment p = 0.036, time p = 0.001; Sidak's multiple-comparisons test: KO_vehicle n = 8, 0 h vs 24 h n.s., 0 h vs 48 h n.s., 24 h vs 48 h n.s.; KO_CTEP n = 11, 0 h vs 24 h **, 0 h vs 48 h **, 24 h vs 48 h n.s.; KO_vehicle vs KO_CTEP 48 h *).