Fig. 3.

Accumulation of ubiquitinated proteins and eosinophilic mitochondrial aggregates in cortical and spinal neurons of transgenic TDP-43 mice. a Ubiquitin pathology in layer V of the motor cortex of both Mt-TAR6/6 and Wt-TAR4/4 mice, which was absent in Ntg mice. Scale bars 50 μm. b In addition, ubiquitinated cytoplasmic inclusions could be observed in (1) Mt-TAR5/6, (2) Mt-TAR6/6 and (3) Wt-TAR4/4 mice. Scale bars 10 μm. Hematoxylin and eosin (H&E) staining of brain and spinal cord showed accumulation of eosinophilic structures (arrows) in large motor neurons of c cortical layer V and d spinal cord of end-stage Mt-TAR6/6, Mt-TAR5/6, and Wt-TAR4/4 mice, which were absent in Ntg control mice. Scale bars 20 μm. e–h Ultrastructural analysis of lumbar spinal cord demonstrated abnormal accumulations of mitochondria of various shapes (insets) in f–g Mt-TAR6/6 and h Wt-TAR4/4 mice compared to e Ntg controls. g Clustered mitochondria were deformed and enlarged with disorganized cristae in Mt-TAR6/6 mice. f and h Insets in the upper right corner show a higher magnification of the boxed region. Scale bars 2 μm