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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Sarm1 deletion suppresses TDP-43-linked motor neuron degeneration and cortical spine loss

Fig. 1

Sarm1 deletion mitigates TDP43Q331K-mediated motor neuron loss and axon degeneration. a. Breeding scheme. b. Nissl-stained lumbar motor neurons of 10-month-old mice. Representative images shown. Scale bar, 50 μm. c. Quantification of Nissl-stained lumbar motor neurons per section at spinal cord L3. (n = 4 NTG; n = 4 Q331K-Sarm1+/−; n = 6 Q331K-Sarm1−/−) ANOVA P = 0.0404. Pairwise comparisons: NTG vs. Q331K-Sarm1+/−: * P = 0.0351; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: * P = 0.0392. d. Representative images showing intact YFP+ axons of L4 ventral roots from mice of three genotypes at different time points. Scale bar 100 μm. e. Quantification of fluorescent axons in wholemount YFP+ L4 ventral roots at different time points. ANOVA Interaction P = 0.0157. Pairwise comparisons: 5 weeks, Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ** P = 0.0026; 3 months, Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ** P = 0.0040; 10 months, Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: * P = 0.0289. f. Percentage of YFP+ axons undergoing fragmentation in L4 ventral roots at different time points. ANOVA Genotype P < 0.0001. Pairwise comparisons: 5 weeks, Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ** P = 0.0014; 3 months, Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.1104; 10 months, NTG vs. Q331K-Sarm1+/−: * P = 0.0464; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.7870. g. Fibre diameters measured at the thickest part of intact YFP+ axons in L4 ventral roots at different time points. ANOVA Interaction P = 0.0051. Pairwise comparisons: 5 weeks, NTG vs. Q331K-Sarm1+/−: ns P = 0.1295; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.2198; 3 months, NTG vs. Q331K-Sarm1+/−: ns P = 0.1567; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.1567; 10 months, Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.1810. h. Distribution of diameters of YFP+ L4 motor axons at 10 months of age. ANOVA Interaction P = 0.0014. Pairwise comparisons: Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: * P = 0.0386. For (e-h) (n = 5 mice per genotype); ****P < 0.0001. For (c) one-way (e-h) two-way ANOVA followed by Holm-Sidak post-hoc test for pairwise comparisons. Error bars represent mean ± s.e.m

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