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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

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

Fig. 3

Neurodegeneration is more prominent in the entorhinal cortex than motor cortex of TDP-43Q331K mice. a-b. Brain weights of mice at different time points. a. Male (n = 6–8 NTG; n = 4–6 Q331K- Sarm1+/−; n = 6–10 Q331K-Sarm1−/−). ANOVA genotype P < 0.0001. Pairwise comparisons: 5 weeks, NTG vs. Q331K-Sarm1+/−: * P = 0.0160; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.5696; 3 months, NTG vs. Q331K-Sarm1+/−: * P = 0.0458; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.9658; 10 months, NTG vs. Q331K-Sarm1+/−: **** P < 0.0001; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.6290. b. Female (n = 5–8 NTG; n = 3–5 Q331K-Sarm1+/−; n = 4–5 Q331K-Sarm1−/−). ANOVA genotype P = 0.0006. Pairwise comparisons: 1 month, NTG vs. Q331K-Sarm1+/−: ns P = 0.3873; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.3283; 4 months, NTG vs. Q331K-Sarm1+/−: ns P = 0.4957; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.8347; 15 months, NTG vs. Q331K-Sarm1+/−: * P = 0.0279; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.5565. c. Brain volumes of female mice at 10 months of age measured by ex vivo MRI (n = 11 NTG; n = 10 Q331K-Sarm1+/−; n = 11 Q331K-Sarm1−/−). ANOVA P < 0.0001. Pairwise comparisons: NTG vs. Q331K-Sarm1+/−: *** P = 0.0001; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.6180. d-e. MRI study-specific template (d. coronal; e. transverse) with an overlay representing voxel-wise volume differences (%) between Q331K-Sarm1+/− and NTG mice at 10 months of age. The colour of the overlay indicates the inter-group volume difference (warm and cool colours represent gain and loss of volume, respectively, ranging from − 25 to 25%), while the transparency indicates the statistical significance, ranging from FWE-corrected p value 0.5 (transparent) to 0 (opaque). Areas in which FWE-corrected p value < 0.05 are contoured in black. (Red arrow – entorhinal cortex; yellow arrow – cingulate cortex) f-g. Representative images of YFP+ neurons from the primary motor cortex (upper) and entorhinal cortex (lower) from mice 10 months of age. Scale bar 200 μm. f. Density of YFP+ neurons in both the primary motor and entorhinal cortex (n = 5 NTG; n = 4 Q331K-Sarm1+/−; n = 5 Q331K-Sarm1−/−). YFP+ neuron density motor cortex: ANOVA P = 0.2661. YFP+ neuron density entorhinal cortex: ANOVA P = 0.0013, Pairwise comparisons: NTG vs. Q331K-Sarm1+/−: *** P = 0.0009; Q331K-Sarm1+/− vs. Q331K-Sarm1−/−: ns P = 0.1079. (a-b) Two-way (c, g) one-way ANOVA followed by Holm-Sidak post-hoc test for pairwise comparisons; error bars represent mean ± s.e.m

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