Fig. 2
FTLD-TDP-GRN extracts induce de novo TDP-43 pathology in CamKIIa-hTDP-43NLSm mice. Representative photomicrographs of p409-410 IHC staining in the cortex (layers I–VI, a–d) and hippocampus (e–n) of injected CamKIIa-hTDP-43NLSm mice at 1 mpi (n = 3) in ipsilateral and contralateral sides of the brain. Higher magnifications of the black-dashed boxes in a, c show p409-410-positive staining in cortical cells in b, d. Arrow in b points to the cell magnified in the inset. e–n show p409-410 immunostaining in the hippocampus: CA1 layer, stratum radiatum (rad), stratum oriens (or), dentate gyrus (DG), and subiculum (Sub). Higher magnifications of the black-dashed boxes in e, h, k, m show CA1 pyramidal cells (f, i), granule cells (Gr) and mossy fibers (MF) (g, j) and Sub (l, n). Arrows in f, g, l point to cells magnified in the insets. o–r show p409-410 and p403-404 IHC staining in adjacent sections of hippocampus from injected CamKIIa-hTDP-43NLSm mice at 1 mpi. p, r show higher magnifications of the black-dashed boxes in o, q, respectively, and arrow points to the same neuron bearing NCIs positive for p409-410 (p) and p403-404 (r). s, t show representative double-label IF images of p409-410 (red) staining and hTDP-43 (s, green) and mouse TDP-43 (t, green). Asterisks in s indicate the primary cytoplasmic distribution of hTDP-43NLSm protein. Panels at the far right depict higher magnifications of the white-dashed boxes in s and t, showing co-localization with aggregates positive for p409-410 (red, white arrow) and hTDP-43NLSm (green, white arrow) or nuclear clearance and reduced recruitment of mTDP-43 (green, white arrow) into p409-410-positive aggregates (red, white arrow). Scale bar = 200 µm (a, c, e, h, k, m), 50 µm (l, m, o, g, s, t) 20 µm (b, d, f, g, i, j) and 10 µm (right panels in s, t and insets)
