Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snail Lymnaea stagnalis.
Cerebral ganglia of the freshwater snail Lymnaea stagnalis were incubated in vitro in 10 microM 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Graduate School Neurosciences, Vrije Universiteit, Faculty of Biology, Amsterdam, The Netherlands.
H H
HH
Boer
C M
CM
Moorer-van Delft
L J
LJ
Müller
B
B
Kiburg
J B
JB
Vermorken
J J
JJ
Heimans
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000473:pathology; D005990:Glycerol / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D008195:Lymnaea; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D017239:Paclitaxel / Q000633:toxicity*; D010446:Peptide Fragments / Q000494:pharmacology; D014677:Pharmaceutical Vehicles
D000927:Anticonvulsants; D000972:Antineoplastic Agents, Phytogenic; D010446:Peptide Fragments; D014677:Pharmaceutical Vehicles; C013765:Org 2766; C000515:cremophor EL; D000324:Adrenocorticotropic Hormone; D017239:Paclitaxel; D005990:Glycerol