Figure 2.

Axonal degeneration and motor neuron apoptosis in A53T mice. Silver staining was used to visualize axonal and neuronal cell body degeneration in brainstem and spinal cord of A53T mice. A, Axonal degeneration in the brainstem of age-matched non-Tg littermates is inconspicuous. The yellow-gold color is the typical background seen with FD NeuroSilver staining. B, The brainstem in A53T mice shows prominent axonal degeneration (black fibers), including axonal swellings (arrow). C, Axonal degeneration in the spinal cord of non-Tg littermates (age, 12–15 months) is minor. The dorsal corticospinal tract (dcs), dorsal lateral funiculus (dlf), and the ventral root (vr) are essentially free of degeneration. D, There is marked axonal degeneration in the dorsal corticospinal tract (dcs), dorsal lateral funiculus (dlf), ventral root (vr), and gray matter in A53T mouse spinal cord. E, Higher-magnification image of silver staining in the dorsal lateral funiculus. The fine black particles are degenerating axons seen in transverse profile. F, Degenerating axonal profiles (black fibers) are seen in the ventral root exit sites in A53T mice. G, Graph showing the quantification of degeneration in the spinal cord of A53T mice killed at early and late stages of disease and in age-matched non-Tg littermate control mice. Values are mean ± SD. ^*p < 0.01 or ^**p < 0.001 (significant difference from control). H, In silver-stained sections of spinal cord, subsets of motor neurons (arrows) undergo somal shrinkage and have a condensing nucleus with round, dark masses of chromatin similar to that seen in apoptosis. Other motor neurons (bottom left and top) appear normal. Scale bars: A, B, 20 μm; C, D, 150 μm; E, F, 32 μm; H, 25 μm.