Changes in shapes of surviving motor neurons in amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis, motor neurons in the spinal cord and brainstem shrink before they die. In 12 cases of sporadic amyotrophic lateral sclerosis, and in 11 control subjects, we have measured the neurons in the second sacral segment and the hypoglossal nucleus, and have calculated a 'shape index' that shows the convexity or concavity of the cell body. (The shape index, SI = 100 x C/P, where C is the circumference of the largest circle that can be inscribed in the neuron and P is the perimeter of the perikaryon, including the bases of the dendrites as seen in a Nissl preparation. The shape index increases with increasing convexity of the cell.) In the ventral horn of segment S2 and in the hypoglossal nucleus, the surviving motor neurons in amyotrophic lateral sclerosis showed significantly decreased size and increased shape index (convexity) of the cell bodies. By contrast, the nucleus of Onuf in segment S2, consisting of neurons that supply the pelvic floor muscles, was preserved in amyotrophic lateral sclerosis. Its cells did not differ significantly in size or convexity between the amyotrophic lateral sclerosis and control groups. In both the hypoglossal and S2 neuronal populations in amyotrophic lateral sclerosis, the sizes of the cells were positively correlated with the numbers of surviving motor neurons. However, there was no correlation of the shape index with numbers of cells. This is interpreted as due to shrinkage of neurons still taking place at the time of death, when the changes in shape were probably largely completed. These observations indicate that the mechanism of neuronal atrophy in amyotrophic lateral sclerosis may involve both reduced protein synthesis and enzymatic degradation of the cytoskeleton within the larger dendrites.