Abstract
This report deals with an ultrastructural investigation of the synapses of anterior horn neurons in the lumbar spinal cords of five patients with amyotrophic lateral sclerosis (ALS) who had mild neuronal depletion. Specimens from five age-matched, neurologically normal individuals served as controls. In each instance, the autopsy was performed within 3 h after death. A statistically significant decrease in cell body area, number of synapses and total synaptic length was found in the normal-appearing neurons of the ALS patients. The alterations were more pronounced in neurons with central chromatolysis. However, despite an approximately 20% reduction in the number of synapses, the length of the active synaptic zone of the normal-appearing neurons in the ALS patients was not diminished. This observation may be accounted for by a plasticity to the loss of synapses which maintained the active zone of the remaining synapses to increase synaptic efficiency. It is suggested that when the plasticity of the active zone reaches its limit, the continuing loss of synapses may lead to functional impairment. The capacity of the active synaptic zone to respond to progressive denervation of the anterior horn neurons may preserve motor function or slow the development of motor deficits in the early stage of degeneration of the lower motor neurons.
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References
Adams I (1987) Comparison of synaptic changes in the precentral and postcentral cerebral cortex of aging humans: a quantitative ultrastructural study. Neurobiol Aging 8: 203–212
Burke RE (1981) Motor units: anatomy physiology, and functional organization. In: Brooks VB (ed) Handbook of physiology. Section I. The nervous system, vol 2, Part 1. American Physiological Society, Bethesda, pp 345–422
Chou SM (1979) Pathognomy of intraneuronal inclusions in ALS. In: Tsubaki T, Toyokura Y (eds) Amyotrophic lateral sclerosis. University of Tokyo Press, Tokyo, pp 135–176
Cragg BG (1975) The density of synapses and neurons in normal, mentally defective and aging human brains. Brain 98: 81–90
Dekosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 27: 457–464
Hillman DE, Chen S (1985) Plasticity in the size of presynaptic and postsynaptic membrane specializations. In: Cotman CW (ed) Synaptic plasticity. Guilford Press, New York, pp 39–76
Hirano A (1982) Aspects of the ultrastructure of amyotrophic lateral sclerosis. In: Rowland LP (ed) Human motor neuron diseases. Raven Press, New York, pp 75–88
Hirano A, Iwata M (1979) Pathology of motor neurons with special reference to amyotrophic lateral sclerosis and related diseases. In: Tsubaki T, Toyokura Y (eds) Amyotrophic lateral sclerosis. University of Tokyo Press, Tokyo, pp 107–133
Huttenlocher PR (1979) Synaptic density in human frontal cortex: developmental changes and effects of aging. Brain Res 163: 195–205
Iwasaki Y (1984) Synaptological study of ventral horn cells in amyotrophic lateral sclerosis. Rinsho Shinkeigaku 24: 205–213
Matsumoto S, Goto M, Kusaka H, Ito H, Imai T (1993) Synaptophysin immunoreactivity in the anterior horn of the spinal cord in amyotrophic lateral sclerosis (abstract). Neuropathology 13 [Suppl]: 898
Petit TL, Le Boutiller JD, Alfano DP, Becker LE (1984) Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex. Exp Neurol 83: 13–23
Pullen AH, Martin JE, Swash M (1992) Ultrastructure of presynaptic input to motor neurons in Onuf's nucleus: controls and motor neuron disease. Neuropathol Appl Neurobiol 18: 213–231
Rees S (1976) A quantitative electron microscopic study of the aging human cerebral cortex. Acta Neuropathol (Berl) 36: 347–362
Rutledge LT (1978) The effects of denervation and stimulation upon synaptic ultrastructure. J Comp Neurol 178: 117–128
Sasaki S, Maruyama S (1994) Decreased synaptophysin immunoreactivity of the anterior horns in motor neuron disease. Acta Neuropathol 87: 125–128
Scheff SW, Price DA (1993) Synapse loss in the temporal lobe in Alzheimer's disease. Ann Neurol 33: 190–199
Scheff SW, Dekosky ST, Price DA (1990) Quantitative assessment of cortical synaptic density in Alzheimer's disease. Neurobiol Aging 11: 29–37
Triller A, Korn H (1982) Transmission at a central inhibitory synapse. III. Ultrastructure of physiologically identified and stained terminals. J Neurophysiol 48: 708–736
Triller A, Korn H (1985) Activity dependent deformations of pre-synaptic grids at central synapses. J Neurocytol 14: 177–192
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Supported by a grant-in-aid for General Scientific Research (C) from the Japanese Ministry of Education, Science and Culture, and a research grant for New Drug Development in ALS from the Ministry of Health and Welfare
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Sasaki, S., Maruyama, S. Synapse loss in anterior horn neurons in amyotrophic lateral sclerosis. Acta Neuropathol 88, 222–227 (1994). https://doi.org/10.1007/BF00293397
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DOI: https://doi.org/10.1007/BF00293397