Ultrastructural study of the synapses of central chromatolytic anterior horn cells in motor neuron disease

This report deals with an ultrastructural investigation of the synapses on the somata of central chromatolytic anterior horn neurons of seven patients with amyotrophic lateral sclerosis (ALS) and four patients with lower motor neuron disease (LMND) who had no upper motor neuron or corticospinal tract involvement. Specimens from 24 age-matched individuals who died of non-neurological diseases served as controls. We examined a total of 171 anterior horn neurons with central chromatolysis (51 from ALS, 42 from LMND and 78 from controls), and 174 normal-appearing anterior horn neurons as controls. The cross-sectional area, the number of synapses, and the length of active zone were significantly reduced in the chromatolytic neurons of both patients and controls as compared with normal-appearing neurons of the controls (p < 0.0001). However, regarding chromatolytic neurons, no significant differences were seen in the number of synapses, length of each individual synapse, and length of its active zone between patients and controls and also in the frequency of presynaptic alterations on the somata. There was no overall difference between ALS and LMND patients in any of these parameters. Our findings suggest that the flow of electrophysiological information from afferent fibers to the somata may be greatly impaired in central chromatolytic neurons of both control individuals and patients with motor neuron disease (MND), and that the observed synaptic alterations may reflect pathological events resulting from anterior horn neuron degeneration. It may represent a compensatory mechanism of the synapses for diminished synaptic function that synapses were relatively well preserved on the somata of central chromatolytic neurons of the MND patients as compared with those of the chromatolytic neurons of the controls despite of markedly reduced cross-sectional area in the former. It also suggests that the pathomechanism involved in central chromatolysis differs between normal individuals and patients with MND.