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. 2022 May 2;25(5):596–606. doi: 10.1038/s41593-022-01052-2

Fig. 4. Activity-dependent myelination contributes to generalized epilepsy progression.

Fig. 4

a, Representative transmission electron micrographs from corpus callosum body of 6-month-old mice. Scale bar, 2 μm. b, g-ratios from 6-month-old Scn8a+/mut and Scn8a+/mut OPC cKO mice. Each dot represents the g-ratio for one axon. c, Mean g-ratios for each mouse. Scn8a+/+, n = 4 mice; Scn8a+/+ OPC cKO, n = 4 mice; Scn8a+/mut, n = 4 mice; Scn8a+/mut OPC cKO, n = 4 mice. One-way ANOVA, F3,12 = 8.753, P = 0.0024. Post hoc Tukey’s test: Scn8a+/mut versus Scn8a+/+, P = 0.0085, Scn8a+/mut versus Scn8a+/+ OPC cKO, P = 0.0042. Scn8a+/mut OPC cKO mice versus Scn8a+/+, P > 0.99. Scn8a+/mut OPC cKO mice versus Scn8a+/+ OPC cKO, P > 0.99. Scn8a+/mut OPC cKO versus Scn8a+/mut mice, P = 0.0066. Scn8a+/+ versus Scn8a+/+ OPC cKO, P = 0.9756. d, Representative seizure in a Scn8a+/mut mouse. e, Continuous EEG recordings showing decreased incidence of seizures (arrowheads) in Scn8a+/mut OPC cKO mice at 6 months. f, Mean seizures per hour for each mouse. 3 months: Scn8a+/+, n = 3 mice; Scn8a+/+ OPC cKO, n = 8 mice; Scn8a+/mut, n = 7, Scn8a+/mut OPC cKO, n = 3 mice. One-way ANOVA: F3,17 = 5.814, P = 0.0063. Post hoc Tukey’s test: Scn8a+/+ versus Scn8a+/mut, P = 0.045. Scn8a+/mut versus Scn8a+/mut OPC cKO, P = 0.6. 4 months: Scn8a+/+, n = 5 mice; Scn8a+/+ OPC cKO, n = 6 mice; Scn8a+/mut, n = 6 mice, Scn8a+/mut OPC cKO, n = 4 mice. One-way ANOVA: F3,17 = 23.05, P < 0.0001. Tukey’s test: Scn8a+/+ versus Scn8a+/mut, P < 0.0001. Scn8a+/mut versus Scn8a+/mut OPC cKO, P = 0.0193. 6 months: Scn8a+/+, n = 5 mice; Scn8a+/+ OPC cKO, n = 5 mice; Scn8a+/mut, n = 5 mice; Scn8a+/mut OPC cKO, n = 4 mice. One-way ANOVA: F3,15 = 11.13, P = 0.0004. Tukey’s test: Scn8a+/+ versus Scn8a+/mut, P = 0.0008. Scn8a+/mut versus Scn8a+/mut OPC cKO, P = 0.0218. g, Schematic of recording electrodes over somatosensory cortices, created with BioRender. h, Representative seizure from a 6-month-old Scn8a+/mut mouse with coherence plot. i, Ictal theta band coherence. Scn8a+/mut, n = 6 mice, Scn8a+/mut OPC cKO, n = 7 mice. Two-tailed t-test: P = 0.047. Each dot represents the mean for one animal (c, f, i), with group means ± s.e.m. Scn8a+/+, black dots; Scn8a+/+ OPC cKO, gray dots; Scn8a+/mut, red dots; Scn8a+/mut OPC cKO, blue dots. *P < 0.05, **P < 0.01, ***P < 0.001, NS, non-significant (P > 0.05).

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