Figure 4.

A–D, Autophagic vacuoles are present in spinal cord dystrophic axons of 20-month-old moca^−/− mice. A, A general view of the wild-type spinal cord showing the normal appearance of myelinated and nonmyelinated axons. B, A closer look at the axonal cytoskeleton and organization showing microtubules (m, arrow) are often in bundles and more irregularly spaced compared with evenly distributed NFs (f, arrow). Mt (blue), Mitochondria. C, A typical axonal swelling showing accumulation of AVs (dashed circle) and a degenerated axon (arrowhead) in the spinal cord of moca^−/− mice. D, Accumulation of AVs. Mt (blue), Mitochondria; 1 (orange), double-membrane autophagosomes representing early stages of autophagy; 2 (blue), residual bodies containing degraded organelles, representing late stages of autophagy; L (pink), lysosomes, before fusion with autopha-gosomes; Ml (yellow), multilaminar body. Scale bars: 2 μm (A, C) or 500 nm (B, D). E–J, Various pathological morphologies of axonal swellings in the spinal cord of 20-month-old moca^−/− mice. E, Disorganized axoplasm. F, Disorganized axonal cytoskeletal components are tangled together, and mitochondria are buried in these abnormal structures. The organelles and AVs accumulate at the edge of the tangled axonal cytoskeleton (arrows). G, Hypertrophy of NFs is shown in the central part of axonal swellings with AVs and organelles accumulated at the edge (arrows). H, Various axoplasmic abnormalities are present in the axonal swelling including a hypertrophic cytoskeleton, organelles, and AVs (arrows). I, An axonal swelling has many vacuoles (V) along with accumulated organelles and AVs (arrows). J, An axonal swelling showing hypertrophic NFs (*f), and diffused organelles and AVs (arrows).