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Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snailLymnaea stagnalis

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Summary

Cerebral ganglia of the freshwater snailLymnaea stagnalis were incubatedin vitro in 10 μM Taxol for 8 and 24 h. Cremophor EL (0.1%) was used as a diluant. The tissue was processed for electron microscopy. Various ultrastructural parameters were assessed quantitatively. Cremophor EL appeared to seriously affect the cell somata of the multipeptidergic caudodorsal cells. In the Cremophor-controls the mean area of Golgi zones, the percentage dense material (neuropeptides) in these zones, the number of large electron dense granules (these are involved in neuropeptide processing) and the mean nuclear heterochromatin clump size, were significantly smaller than in the Ringer-controls, whereas the number of lipid droplets was higher. All these parameters, except for the lipid droplets, were not different in the Cremophor-controls and the Taxol-treated specimens. After 24 h treatment, but not after 8 h, Cremophor EL furthermore induced an increase in the number of axonal microtubules. It is argued that the results might signify activation of the neurons by Cremophor EL. Taxol induced a significant increase in the number of microtubules in axons and cell somata. Furthermore an increase in the number of Golgi zones was observed, suggesting activated neuropeptide synthesis. In all groups immunostaining with antibodies to neuropeptides produced by the caudodorsal cells was normal. Release of neuropeptide (exocytosis) from axon endings was elevated after Taxol treatment, and exceptionally high in specimens cotreated with Taxol and Org 2766 (incubation time 22 h). The effect of Org 2766 and Taxol on the number of microtubules was cumulative. It is argued that transport of neuropeptide granules from the cell somata to the axon terminals was not affected by Taxol. It is concluded that Taxol neurotoxicity is probably not due to impeded microtubular axonal transport.

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Authors and Affiliations

  1. Faculty of Biology, Graduate School Neurosciences, Amsterdam, Research Institute Neurosciences, Vrije Universiteit, De Boelelaan 1087, 1081, HV Amsterdam, The Netherlands

    H. H. Boer, Carry M. Moorer-van Delft, Linda J. Müller & Barbara Kiburg

  2. Department of Oncology, Vrije Universiteit Hospitaal, P. O. Box 7057, 1007, HB Amsterdam, The Netherlands

    J. B. Vermorken

  3. Department of Neurology, Vrije Universiteit Hospitaal, P. O. Box 7057, 1007, HB Amsterdam, The Netherlands

    J. J. Heimans

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  1. H. H. Boer
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  2. Carry M. Moorer-van Delft
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  3. Linda J. Müller
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  5. J. B. Vermorken
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  6. J. J. Heimans
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Boer, H.H., Moorer-van Delft, C.M., Müller, L.J. et al. Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snailLymnaea stagnalis . J Neuro-Oncol 25, 49–57 (1995). https://doi.org/10.1007/BF01054722

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