Fig. 3: Thyromimetic treatment enhances oligodendrocyte gain during remyelination.

A Hydrolysis of LL-341070 into its active form by CNS-enriched fatty acid amide hydrolase (FAAH). B Experimental timeline. C Treatment groups. D Cumulative OL loss and gain (as a percentage of baseline OLs) in individual mice over time (vehicle: n = 7, 0.1 mg/kg: n = 7, 0.3 mg/kg: n = 6). E Cumulative OL loss by 3 weeks does not differ between groups in mean or variance. F Representative images of V1 OLs at 1.5 weeks post-cuprizone. Locations of lost OLs (dark blue) and new OLs (light blue) are encircled. Additional timepoints in Supplementary Fig. 7. G ANCOVA with unequal slopes shows effect of treatment, cumulative OL loss, and interaction between cumulative OL loss and treatment on cumulative OL gain at 1.5 weeks. H High dose LL-341070 increases cumulative OL gain at 1.5 weeks. Low dose LL-341070 increases cumulative OL gain after 7 weeks. I High dose LL-341070 increases maximum OL gain rate (as a percentage of baseline OLs/day) during remyelination. J High dose LL-341070 increases OL gain rate (as a percentage of baseline OLs/day) only between 0 and 1.5 weeks. In (E), ANOVA (F(2, 14) = 0.29, p = 0.75). Brown-Forsythe (F(2, 14) = 1.05, p = 0.37). Vehicle: n = 7; 0.1 mg/kg: n = 7; 0.3 mg/kg: n = 6. In (G), ANCOVA with unequal slopes (F(5, 18) = 9.5, ***p = 0.0001). Effects: treatment (F = 7.91, **p = 0.0034), OL loss (F = 23.33, ***p = 0.0001), interaction (F = 6.41, **p = 0.0079). Vehicle: n = 8, 0.1 mg/kg: n = 9, 0.3 mg/kg: n = 7. In (H) 1.5w, Tukey’s HSD (0.3 mg/kg vs. vehicle: **p = 0.0025; 0.3 mg/kg vs. 0.1 mg/kg: *p = 0.049). Vehicle: n = 8, 0.1 mg/kg: n = 9, 0.3 mg/kg: n = 7. In (H) 3w, Tukey’s HSD (0.3 mg/kg vs. vehicle: p = 0.055). Vehicle: n = 7, 0.1 mg/kg: n = 7, 0.3 mg/kg: n = 6. In (H) 7w, Tukey’s HSD (0.3 mg/kg vs. vehicle, p = 0.051; 0.1 mg/kg vs. vehicle, *p = 0.034). Vehicle: n = 5, 0.1 mg/kg: n = 4, 0.3 mg/kg: n = 5. In (I), Tukey’s HSD (0.3 mg/kg vs. vehicle: *p = 0.018). Vehicle: n = 7, 0.1 mg/kg: n = 7, 0.3 mg/kg: n = 6. In (J) 0-1.5w, Tukey’s HSD (0.3 mg/kg vs. vehicle: **p = 0.0012; 0.3 mg/kg vs. 0.1 mg/kg: *p = 0.025). Vehicle: n = 8, 0.1 mg/kg: n = 9, 0.3 mg/kg: n = 7. In (J) 1.5-3w, ANCOVA with unequal slopes in Supplementary Fig. 8G not significant. Vehicle: n = 7; 0.1 mg/kg: n = 7; 0.3 mg/kg: n = 6. In (J) 3-5w, ANCOVA with unequal slopes in Supplementary Fig. 8H not significant. Vehicle: n = 6, 0.1 mg/kg: n = 4, 0.3 mg/kg: n = 5. *p < 0.05, **p < 0.01; least square mean ± SEM in (H–J); n=mice; two-sided statistical tests. See Supplementary Data 1 for statistical details and Source Data file for source data. OL=oligodendrocyte, V1=primary visual cortex.