Skip to main content
. 2006 Jan 4;26(1):41–50. doi: 10.1523/JNEUROSCI.4308-05.2006

Figure 5.

Figure 5.

Neuronal cell death in A53T mice. A, B, Nuclear DNA fragmentation, identified by TUNEL, was detected in brainstem (A, arrow), sensorimotor cortex (B, arrows), and spinal motor neurons (data not shown) in A53T mice at early and end-stage disease. C, Subsets of spinal motor neurons had intracytoplasmic TUNEL seen as granules (arrow) that subsequent TUNEL–immunogold EM revealed to be mitochondria (inset). A–C, TUNEL preparations counterstained with cresyl violet. D, E, Subsets of large neurons in brainstem (D, arrow) and spinal motor neurons (E, arrow) displayed cleaved caspase-3 immunoreactivity indicative of apoptosis. F, Graph showing the quantification of dying cells (determined by TUNEL) in the brainstem retrorubal field and pontine reticular formation of A53T mice killed at early and late stages of disease and in non-Tg control mice. Values (cells per square millimeter) are mean ± SD. *p < 0.05 or **p < 0.01 (significant difference from control). G, Graph showing the quantification of the number of cleaved caspase-3 immunopositive cells in the brainstem retrorubal field and pontine reticular formation of A53T mice killed at early and late stages of disease and in non-Tg control mice. Values (cells per square millimeter)are mean ± SD. *p < 0.05 or **p < 0.01 (significant difference from control). H, p53 was not detected in spinal motor neurons in 12- to 15-month-old non-Tg mice. I, Subsets of spinal motor neurons in A53T mice accumulated p53 (arrows), but other motor neurons were not positive for p53 (bottom left). J, EM on A53T mouse spinal cord revealed the presence of degenerating cells with a nuclear morphology consistent with apoptosis (white asterisk). The nucleus is condensed into a uniformly dense round mass. K, L, Immunogold EM for p53 in spinal motor neurons showed that in age-matched non-Tg mice, p53 was at a low level in the cytoplasm (K, arrows) and was associated rarely with the mitochondria; in contrast, in A53T mice, p53 was associated with the outer mitochondrial membrane (L, arrows). Scale bars: A, 8 μm; B, 10 μm; C, 12 μm (inset, 0.18 μm); D, E, 22 μm; H, I, 22 μm; J, 2.5 μm; K, L, 6.5 μm.