Fig. 3: Astrocytic Nrf2 activation regulates oligodendrocyte survival and remyelination.
From: Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration
a GFAP-Nrf2 maintain Nrf2 pathway activation in astrocytes. b Mean FPKM values ± s.e.m. of Nrf2-target genes. two-tailed ratio paired t-test between wildtype and GFAP-Nrf2 mice in no-lesion conditions, P value = 0.0003, t = 8.809. n = 6 mice/condition (WT), n = 5 mice/condition (GFAP-Nrf2). c HMOX1+ (magenta) astrocytes (GFAP+) (arrows) in the non-lesioned corpus callosum. Hoechst in cyan. Scale bar, 25 μm. d Mean GFAP+ cells/mm2 ± s.e.m. Two-tailed Mann–Whitney test, wildtype (WT) vs GFAP-Nrf2 in no lesion P = 0.3810, two-tailed unpaired Student’s t-test with Welch’s correction, WT vs GFAP-Nrf2, 3 DPI P = 0.0089 t = 53.371, 7 DPI P = 0.0591 t = 3.711, 10 DPI P = 0.5754 t = 0.5791. n = 3 mice/group (GFAP-Nrf2 no lesion, Wildtype and GFAP-Nrf2 3 and 7 DPI LPC), n = 6 mice/group (Wildtype no lesion, Wildtype and GFAP-Nrf2 14 DPI). e GFAP+ astrocytes (yellow) in the lesioned corpus callosum (outlined). Scale bar, 100 μm. f HMGCS1+ (magenta) GFAP+ astrocytes (yellow)(arrows) in lesioned corpus callosum. Hoechst in cyan. Scale bar, 50 μm. g Mean HMGCS1 + GFAP+ cells/mm2 ± s.e.m.. Two-tailed unpaired Student’s t-test with Welch’s correction WT vs GFAP-Nrf2, 7 DPI P = 0.0482 t = 2.823, 14 DPI P = 0.3112 t = 1.1. n = 3 mice/condition (7 DPI), n = 4 mice/condition (14 DPI wildtype), n = 7 mice/condition (14 DPI GFAP-Nrf2). h Mean FDPS + GFAP+ cells/mm2 ± s.e.m. Two-tailed unpaired Student’s t-test with Welch’s correction WT vs GFAP-Nrf2, 7 DPI P = 0.0398 t = 3.179, 14 DPI P = 0.2842 t = 1.148. n = 3 mice/condition (7 DPI), n = 4 mice/condition (wildtype 14 DPI), n = 7 mice/condition (GFAP-Nrf2 14 DPI). i Mean percentage of GFAP+ cells positive for HMGCS1 ± s.e.m. Two-tailed unpaired Student’s t-test with Welch’s correction WT vs GFAP-Nrf2, 7 DPI P < 0.0001 t = 10.11, 14 DPI P = 0.1952 t = 1.469. n = 5 mice/condition (wildtype 7 DPI), n = 4 mice/condition (GFAP-Nrf2 7 DPI, wildtype 14 DPI), n = 6 mice/condition (GFAP-Nrf2 14 DPI). j MBP (magenta) in the corpus callosum (outlined). Scale bar; 100 μm. k Percentage MBP area ± s.e.m. Two-tailed unpaired Student’s t-test with Welch’s correction WT vs GFAP-Nrf2, no lesion P = 0.6985 t = 0.4244, 14 DPI P = 0.0225 t = 3.047, 21 DPI P = 0.0024 t = 9.212. n = 3 mice/condition (GFAP-Nrf2 no lesion, Wildtype 21 DPI LPC), n = 4 mice/condition (GFAP-Nrf2 21 DPI LPC), n = 5 mice/condition (GFAP-Nrf2 14 DPI LPC) n = 6 mice/condition (Wildtype no lesion, 14 DPI LPC). l Mean Olig2+ cells/mm2 ± s.e.m. Two-tailed unpaired Student’s t-test with Welch’s correction WT vs GFAP-Nrf2, no lesion P = 0.3603 t = 0.9591, 14 DPI P = 0.0204 t = 2.777. n = 6 mice/condition. m Mean CC1+Olig2+ cells/mm2 ± s.e.m. Two-tailed unpaired Student’s t-test with Welch’s correction WT vs GFAP-Nrf2, no lesion P = 0.4435 t = 0.865, 14 DPI P = 0.0425 t = 2.508. n = 6 mice/condition. n Proportion of Olig2+ cells that are CC1+ (green) or negative (magenta) ± s.e.m. n = 6 mice/condition. Two-way ANOVA with Bonferroni correction, WT vs GFAP-Nrf2; no lesion, CC1+Olig2+ P = 0.8323 CC1-Olig2+ P = 0.8322, two-way ANOVA summary (Interaction F(1,20) = 1.379, P value = 0.2541; Genotype F(1,20) = 3.171 × 10−9, P value >0.9999; Cell type F(1,20) = 242.9, P value <0.0001). 14 DPI, CC1+Olig2+ P = 0.6945 CC1-Olig2+ P = 0.6945, ANOVA summary (Interaction F(1,20) = 1.853, P value = 0.1885; Genotype F(1,20) = 0, P value >0.9999; Cell type F(1,20) = 14.81, P value = 0.0010). o Mean percentage of Olig2+ cells which are cleaved Caspase-3+ ± s.e.m., at 3 DPI, two-tailed Mann–Whitney test, P = 0.8857; at 7 DPI, two-tailed unpaired Student’s t-test with Welch’s correction P = 0.0044, t = 4.49. n = 4 mice/condition (3 DPI), n = 5 mice/condition (GFAP-Nrf2 7 DPI), n = 6 mice/condition (wildtype 7 DPI). Source data is provided with this paper. The image in 3a was created with Biorender.com.
