Fig. 6
TDP-43 mislocalization increases seeding efficiency and spread of pathology. Representative photomicrographs of p409-410 IHC staining in the cortex and hippocampus of CamKIIa-208 (a, d), CamKIIa-hTDP-43NLSm (b, e) and B6C3HF1 (c, f) mice at 1 mpi. Insets are higher magnifications of white framed areas. Arrows and arrowhead points to p409-410-positive NCIs and dendrites, respectively. g, h Plot shows number of p409-410-positive cells in the cortex and hippocampus in Ipsi and Contra sides of CamKIIa-208 (blue bars) and B6C3HF1 mice (red bars) at 1 and 9 mpi. Bar plots show mean and whiskers s.e.m., with individual points representing different mouse overlaid as black circles. Two-way ANOVA followed by a Sidak’s multiple comparisons test was used to compare time points (Factor, P value (F, degrees of freedom)); in g CamKIIa-208 (Cx): side P = 0.019 (8.55, 1), time P = 0.020 (8.32, 1), and interaction P = 0.137 (2.72, 1); B6C3HF1 (Cx): side P = 0.008 (11.97, 1), time P = 0.028 (7.12, 1), and interaction P = 0.105 (3.32, 1). In h CamKIIa-208 (Hp): side P < 0.0001 (85.98, 1), time P < 0.0001 (81.74, 1), and interaction P < 0.0001 (77.6, 1); B6C3HF1 (Hp): side P < 0.0001 (94.6, 1), time P < 0.0001 (78.8, 1), and interaction P < 0.0001 (65.69, 1). ∗P < 0.05, ∗∗∗∗P < 0.0001. Two-way ANOVA followed by Sidak’s multiple comparisons test was used to compare genotypes; in g Cx (ipsi); genotype P = 0.007 (11.71, 1), time P = 0.010 (10.42, 1), and interaction P = 0.008 (3.78, 1); Cx (contra): genotype P = 0.033 (6.26, 1), time, P = 0.041 (5.63, 1), and interaction P = 0.0456 (5.37, 1). In h Hp (Ipsi): genotype P = 0.054 (4.88, 1), time P = 0.002 (17.57, 1), and interaction P = 0.483 (0.53, 1); Hp (contra): genotype P = 0.107 (3.20, 1), time P = 0.038 (5.86, 1), and interaction P = 0.119 (2.95, 1). #P < 0.05. i–o show p409-410 immunostaining in areas distal from the injection site in CamKIIa-208 mice at 9 mpi. Higher magnifications of black framed areas in i and l show p409-410 NCIs in cingulate cortex (j), caudate putamen (Cp) (k), superficial and deep cortical layers (m, n, respectively), and lateral entorhinal cortex (Lent) (o). Arrows in j and k point to p409-410-positive neurons magnified in insets. Scale bar = 200 µm (i, l), 50 µm (j, k) and 10 µm (m–o and insets)
