Summary
The aim of this study was to define morphological and neurophysiological features of an age-related neuropathy in mice and to explore possible underlying pathogenetic mechanisms. Teased-fibre analysis of sciatic nerves in aged animals demonstrated a high incidence of demyelination. Electron microscopic analysis of sciatic nerve also revealed axonal atrophy. Both forms of pathology preferentially effect large myelinated fibres. The morphological evidence suggests that demyelination may have resulted from two processes; a primary event and a late consequence of axonal shrinkage. A high-affinity ouabain-binding form of (Na+, K+) ATPase was found in both mice sciatic nerve and spinal roots. A progressive and ultimately severe reduction of enzyme concentration with age was demonstrated in sciatic nerve and dorsal root. Since no change with age was seen in fast (anterograde or retrograde) axoplasmic flow, reduced peripheral nerve (Na+,K+) ATPase is not due to impaired enzyme translocation. Motor nerve conduction velocity decreased significantly with age, while minimum F-wave latency and somatosensory evoked potential latency increased. Impaired conduction velocities in aged animals may be attributed to the interaction of many factors including demyelination, remyelination, a disproportionate loss of large myelinated fibres, axonal atrophy, nerve regeneration and reduced peripheral nerve (Na+,K+)ATPase. It is concluded that the neuropathy in senescent mice is not species specific and is less severe, even in long-lived mice species, compared with that seen in the rat.
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Supported by grants from Health Research Council of New Zealand and New Zealand Neurological Foundation
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Robertson, A., Day, B., Pollock, M. et al. The neuropathy of elderly mice. Acta Neuropathol 86, 163–171 (1993). https://doi.org/10.1007/BF00334883
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DOI: https://doi.org/10.1007/BF00334883