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. 2023 Jun 8;14:3372. doi: 10.1038/s41467-023-39046-8

Fig. 4. Stimulating the cholesterol biosynthesis pathway rescues oligodendrocyte survival and remyelination when astrocytic Nrf2 activation is sustained.

Fig. 4

a Proteomics of wildtype lesions at 7 DPI vs no lesion control (CT), represented as Log2FC of 7 DPI/CT. The two-tailed paired t-test between normalised intensities, P value = 0.0012, t = 5.228. n = 3 mice/condition. b Astrocyte-associated proteins in lesions at 7 DPI vs CT, represented as Log2FC. The two-tailed paired t-test between normalised intensities, P value = 0.0217, t = 3.291. n = 3 mice/condition. c Mean FPKM value ± s.e.m. of Abca1. DESeq2 Benjamini–Hochberg test, adjusted P value aP = 0.042. n = 3 mice/condition. d Percentage of GFAP+ cells expressing ABCA1 ± s.e.m. One-way ANOVA with Tukey´s multiple comparisons test; aP = 0.0237, bP = 0.0054, cP = 0.0245. ANOVA summary (F = 6.456 and P value = 0.0031). n = 3 mice/condition (no lesion), n = 4 mice/condition (3, 7, 14 DPI), n = 5 mice/condition (10 DPI). e Percentage of ABCA1+ cells expressing GFAP ± s.e.m. One-way ANOVA with Tukey´s multiple comparisons test; aP = 0.0126, bP = 0.0496. ANOVA summary (F = 9.985 and P value = 0.0004). n = 3 mice/condition (no lesion), n = 4 mice/condition (3, 7, 14 DPI), n = 5 mice/condition (10 DPI). f CS-6253 or PBS was administered daily to LPC-lesioned GFAP-Nrf2 mice from 7–14 DPI. g HMGCS1+ (magenta) astrocytes (GFAP+; yellow) (arrows). Hoechst in cyan. Scale bar, 25 μm. h Percentage of GFAP+ cells expressing HMGCS1 ± s.e.m., two-tailed Mann–Whitney test, aP = 0.0286. n = 4 mice/condition. i Mean Olig2+ cells/mm2 ± s.e.m., two-tailed unpaired Student’s t-test with Welch’s correction, aP = 0.0413, t = 2.61. n = 4 mice/condition. j Mean CC1+Olig2+ cells/mm2 ± s.e.m., two-tailed unpaired Student’s t-test with Welch’s correction, aP = 0.0432, t = 2.555. n = 4 mice/condition. k Proportion of Olig2+ cells which were CC1+ (green) or CC1- (magenta) ± s.e.m. Two-way ANOVA with Bonferroni correction PBS vs CS-6253, CC1+Olig2+ P value = 0.1597, CC1-Olig2+ P value = 0.1734. ANOVA summary (Interaction F(1,12) = 7.141, P value = 0.0203; Condition F(1,12) = 0.001127, P value = 0.9738; Cell type F(1,12) = 24.77, P value = 0.0003). n = 4 mice/group. l Oligodendrocyte lineage cells (Olig2+; yellow) which are mature (CC1+; magenta)(arrows). Hoechst in cyan. Scale bar, 50 μm. m Percentage of CC1+ cells expressing active caspase-3 (Ca3+) ± s.e.m., two-tailed unpaired Student’s t-test with Welch’s correction, aP = 0.0005, t = 6.007. n = 5 mice/condition (PBS) and n = 6 mice/condition (CS-6253). n Myelin basic protein (MBP; magenta) in corpus callosum lesions (outlined). Scale bar, 100 µm. o Percentage MBP area ± s.e.m., two2-tailed Mann–Whitney test, aP = 0.0260, n = 6 mice/condition. Source data is provided with this paper. The image in 4f was created with Biorender.com.