Study of Axonal Dystrophy. I. Pathology of the Neuropil of the Gracile and the Cuneate Nuclei in Ageing and Old Rats: A Stereological Study

Abstract

The changes with age in the neuropil of the gracile and the cuneate nuclei of rats were studied using stereological techniques, in relation to the occurrence of axonal dystrophy. The following were found: (1) significant difference in the volume fraction of presynaptic boutons between the gracile and the cuneate nuclei throughout the whole life span (17% and 13% respectively at 100 days of age); (2) progressive decrease in the volume fraction (34% decrease in the gracile nucleus between 100 and 800 days of age) and in the numerical density of presynaptic boutons, the decline being evident as soon as the animals reached maturity and before axonal dystrophy became manifest; (3) significant differences in the volume fractions of dendrites and of nerve cell bodies between the two nuclei throughout the whole life span of the animals, both being greater in the cuneate than in the gracile nucleus; an age-related decrease in the volume fraction of dendrites was also suspected in the gracile nucleus; (4) progressive increase in the volume fraction of fibrous astrocytic processes (from 3% at 100 days to 10.5% at 800 days in the gracile nucleus); (5) the above described age-related changes of presynaptic boutons and fibrous astrocytic processes were significant only in the gracile nucleus, not in the cuneate. The loss of boutons in ageing gracile nuclei was partially reflected in the appearance of degenerating nerve fibres in ageing gracile tract in the rostral cervical cord. Involutional loss of boutons and dystrophic formation of spheroids both appear and progress closely related in time and space. It was suggested that this set of changes can be understood as one integrated whole in which axonal dystrophy may represent only one side of the coin. The question of the causal mechanisms of axonal dystrophy still remains unanswered.

Upregulation of GFRα-1 and c-ret in primary sensory neurons and spinal motoneurons of aged rats

“…However, the loss of motor and sensory neurons is small also in very old individuals (ϳ10%-20%), and may not explain the behavioral deficits Tomlinson and Irving, 1977;Johnson et al, 1995;Bergman and Ulfhake, 1998;Johnson and Duberley, 1998). It seems more likely that axon lesions, which are widespread in both sensory and motor nerves, represent the structural correlate (Seitelberger, 1952;Johnson et al, 1975;Fujisawa and Shiraki, 1978;Fujisawa, 1988;Krinke, 1983;Schmidt et al, 1995;Kullberg et al, 1998). Furthermore, aged spinal motoneurons and primary sensory neurons show changes in the expression of several molecules indicating axon lesions Bergman et al, 1996).…”

Upregulation of GFRα‐1 and c‐ret in primary sensory neurons and spinal motoneurons of aged rats

“…However, the loss of motor and sensory neurons is small also in very old individuals (ϳ10%-20%), and may not explain the behavioral deficits Tomlinson and Irving, 1977;Johnson et al, 1995;Bergman and Ulfhake, 1998;Johnson and Duberley, 1998). It seems more likely that axon lesions, which are widespread in both sensory and motor nerves, represent the structural correlate (Seitelberger, 1952;Johnson et al, 1975;Fujisawa and Shiraki, 1978;Fujisawa, 1988;Krinke, 1983;Schmidt et al, 1995;Kullberg et al, 1998). Furthermore, aged spinal motoneurons and primary sensory neurons show changes in the expression of several molecules indicating axon lesions Bergman et al, 1996).…”

Immunohistochemical evidence for the selective involvement of dorsal root fibres in Friedreich's ataxia

“…In some areas of the gracile nucleus from the 49-year-old patient, synaptophysin-positive puncta were markedly decreased and some enlarged synaptophysin-positive dystrophic axons were observed (Figure 2d). These immunoreactive dystrophic axons may be due to ageing and not to the pathological process of the disease since they were not seen in the younger patient (Fujisawa & Shiraki, 1978).…”