Journal of Neurocytology

, Volume 14, Issue 1, pp 157–175 | Cite as

Taxol-induced neuropathy: further ultrastructural studies of nerve fibre changesin situ

  • Matias Röytta
  • Cedric S. Raine


Nerve fibre changes have been further monitored morphologically in rat sciatic nerves which had been locally injected with taxol, an antimitotic drug known to promote microtubule assembly. Taxol caused a slowly progressive accumulation of microtubules over a three week period of experimentation, the effect being more pronounced in Schwann cells. Schwann cells of myelinated fibres became detached from nodes of Ranvier and were applied to naked internodes as bulbous cells replete with microtubules and smooth endoplasmic reticulum (ER). In some cases, the smooth ER was believed to arise from rough ER after the displacement of ribosomes. These cells also contained myelin fragments from the original internodes. Microtubules displayed unique relationships with cytoplasmic membranes and were seen to exist as regular 22 nm microtubules, as obliquely sectioned profiles or as incomplete, trough-shaped structures. Internodes devoid of myelin were common, and naked axons covered only by basal lamina appeared swollen and invariably contained an abundance of microtubules. Schwann cells lacking axons had multilobate nuclei and possessed complex arrays comprising smooth ER membranes and microtubules. In areas where microtubules were absent, these membranes compacted to form intracellular myelin. Intermediate filaments existed in lower numbers than normal within both axons and Schwann cells. Arrested mitoses were occasionally seen and it is speculated that together with the immobilization of the cell by the over-abundant polymerization of tubulin, incomplete mitosis was an underlying cause for the observed lack of remyelination over the 21-day period of study. These results suggest that perturbations in microtubule synthesis might dramatically affect Schwann cell behaviour and myelin proliferation.


Sciatic Nerve Schwann Cell Taxol Rough Endoplasmic Reticulum Myelinated Fibre 
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  1. Cajal, S. R. Y. (1928)Degeneration and Regeneration of the Nervous System. Reprinted by Hafner, New York,1, 198–313 (1959).Google Scholar
  2. De Brabander, M. G., Gueuns, G., Nuydens, R., Willebords, R. &Demey, J. (1982) Microtubule stability and assembly in living cells: The influence of metabolic inhibitors, taxol and pH.Cold Spring Harbor Symposium on Quantitative Biology 46, 227–40.Google Scholar
  3. Griffin, J. W. &Price, D. L. (1981) Demyelination in experimental B,B1-iminodipropionitrile and hexacarbon neuropathies. Evidence for an axonal influence.Laboratory Investigation 45, 130–41.PubMedGoogle Scholar
  4. Heath, J. W., Ueda, S., Bornstein, M. B., Daves, G. D. &Raine, C. S. (1982) Buckthorn neuropathyin vitro: Evidence for primary neuronal effect.Journal of Neuropathology and Experimental Neurology 41, 204–20.PubMedGoogle Scholar
  5. Jones, H. B. &Cavanagh, J. B. (1983) Distortions of the nodes of Ranvier from axonal distension by filamentous masses in hexacarbon intoxication.Journal of Neurocytology 12, 436–58.Google Scholar
  6. Masurovsky, E. B., Peterson, E. R., Crain, S. M. &Horwitz, S. B. (1981a) Morphologic alterations in satellite and Schwann cells after exposure of fetal mouse dorsal root ganglia-spinal cord cultures to taxol.International Research Communications Service;Medical Science 9, 968–9.Google Scholar
  7. Masurovsky, E. B., Peterson, E. R., Crain, S. M. &Horwitz, S. B. (1981b) Microtubule arrays in taxol-treated mouse dorsal root ganglion spinal cord cultures.Brain Research 217, 392–8.PubMedGoogle Scholar
  8. Masurovsky, E. B., Peterson, E. R., Crain, S. M. &Horwitz, S. B. (1982) Taxol-induced microtubule formations in fibroblasts of fetal mouse dorsal-root-ganglion-spinal cord cultures.Biology of the Cell 46, 213–16.Google Scholar
  9. Masurovsky, E. B., Peterson, E. R., Crain, S. M. &Horwitz, S. B. (1983) Morphological alterations in dorsal root ganglion neurons and supporting cells of organotypic mouse spinal cord — ganglion cultures exposed to taxol.Neuroscience 10, 491–509.PubMedGoogle Scholar
  10. Parness, J. &Horwitz, S. B. (1981) Taxol binds to polymerized tubulinin vitro.Journal of Cell Biology 9, 479–87.Google Scholar
  11. Peters, A., Palay, S. L. &Webster, H. DeF. (1976)The Fine Structure of the Nervous System: The Cells and their Processes. Philadelphia: W. B. Saunders.Google Scholar
  12. Raine, C. S. (1977a) Morphological aspects of myelin and myelination. InMyelin (edited byMorell, P.), pp. 1–49. New York: Plenum.Google Scholar
  13. Raine, C. S. (1977b) Schwann cell responses during recurrent demyelination and their relevance to onion bulb formation.Neuropathology and Applied Neurobiology 3, 453–70.Google Scholar
  14. Raine, C. S. (1982) Differences in the nodes of Ranvier of large and small diameter fibres in the P.N.S.Journal of Neurocytology 11, 935–47.PubMedGoogle Scholar
  15. Raine, C. S., Ghetti, B. &Shelanski, M. L. (1971) On the association between microtubules and mitochondria within axons.Brain Research 34, 389–93.PubMedGoogle Scholar
  16. Raine, C. S. &Schaumburg, H. H. (1977) The neuropathology of myelin diseases. InMyelin (edited byMorell, P.), pp. 271–322. New York: Plenum.Google Scholar
  17. Röytta, M., Horwitz, S. B. &Raine, C. S. (1984) Taxol-induced neuropathy: short-term effects of local injection.Journal of Neurocytology 13 685–701.PubMedGoogle Scholar
  18. Schiff, P. B., Fant, J. &Horwitz, S. B. (1979) Promotion of microtubule assemblyin vitro by taxol.Nature (London) 277, 665–7.Google Scholar
  19. Schiff, P. B. &Horwitz, S. B. (1980) Taxol stabilizes microtubules in mouse fibroblast cells.Proceedings of the National Academy of Sciences, USA 77, 1561–5.Google Scholar
  20. Tokunaka, S., Friedman, T. M., Toyama, Y., Pacifici, M., &Holzer, H. (1983) Taxol induces microtubule-rough endoplasmic reticulum complexes and microtubule-bundles in cultured chondroblasts.Differentiation 24, 39–47.PubMedGoogle Scholar
  21. Wani, M. C., Taylor, H. I., Wall, M. E., Coggon, P. &McPhail, A. T. (1971) Plant anti-tumor agents, VI. The isolation and structure of taxol: a novel anti-leukemic and anti-tumor agent fromTaxus brevifolia.Journal of the American Chemical Society 93, 2325–7.PubMedGoogle Scholar

Copyright information

© Chapman and Hall Ltd. 1985

Authors and Affiliations

  • Matias Röytta
    • 1
  • Cedric S. Raine
    • 1
  1. 1.Departments of Pathology (Neuropathology) and Neuroscience, and the Rose F. Kennedy Center for Research in Mental Retardation and Human DevelopmentAlbert Einstein College of MedicineThe BronxUSA

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