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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Mice deficient in the C-terminal domain of TAR DNA-binding protein 43 develop age-dependent motor dysfunction associated with impaired Notch1−Akt signaling pathway

Fig. 3

TDP-∆C knock-in mice show mild age-dependent motor dysfunction. a and b Rotarod performances of wild-type mice (WT, n = 16 (male: 11, female: 5)) and TDP-∆C mice (∆C, n = 12 (male: 5, female: 7)) were evaluated every month. Mean holding times on a rotating rod at the indicated ages are plotted with SD. The rotarod performance of TDP-∆C mice did not differ from WT until 18 months of age (a), but declined substantially at 19 and 20 months old (b). Asterisks represents p < 0.05. c and d The number of presynaptic terminals of C-boutons (C, arrows), represented by choline acetyl transferase (ChAT)-positive puncta surrounding motor neurons, was specifically reduced in 700-day-old TDP-∆C mice (c). Representative immunofluorescence images of lumbar motor neurons with C-boutons in 700-day-old WT and TDP-∆C mice stained with antibodies for ChAT and Kv2.1 along with the merged images. Loss of ChAT immunoreactivity on the C-boutons was also confirmed by fluorescent intensity profile (d). Scale bars: 20 μm. e and f The numbers of intact C-boutons per motor neuron (e) and motor neurons per each anterior horn (AH) (f) in lumbar spinal cord (LSC) of 700-day-old WT and TDP-∆C mice with indicated genotypes are shown. For quantification, more than 50 motor neurons (e) and 30 AHs (f) in three animals per genotype were counted, and the data are plotted as mean ± SD. g Gliosis of glial fibrillary acidic protein (GFAP)-positive astrocytes was slightly more intense in the LSC of 700-day-old TDP-∆C mice compared to age-matched WT. Representative immunofluorescence images of LSC sections from WT and TDP-∆C mice stained using anti-Iba1 (microglial marker, red) and anti-GFAP (astrocytic marker, green) antibodies, along with merged images. Sections were also counterstained with DAPI staining (blue). Scale bars: 20 μm

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