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Microtubule-mitochondrial associations in regenerating axons after taxol intoxication
C S Raine1, M Röytta, M Dolich
1Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
Abstract:
Ultrastructural examination of regenerating axons within rat sciatic nerve injected locally with the microtubule assembly-promoting compound, taxol, has revealed the frequent association of microtubules with axoplasmic organelles, in particular mitochondria. This was characterized by the prodigious accumulation of axonal microtubules, some of which became aligned to form multilayered channels within which axoplasmic organelles were sequestered. Between each layer of microtubules forming the walls of these channels, a 5 nm filament, believed to derive from microtubule side-arm material, was present. The findings suggest that these microtubule channels might play a role in mitochondrial traffic across the lesion area. Similar but much less elaborate associations within axons between microtubules and axoplasmic organelles, including mitochondria, have been described previously. Within regenerating axonal sprouts, intermediate filaments were found only at later timepoints when they commonly occurred within the microtubule channels. It is proposed that taxol impedes axonal regrowth at an early stage of cytoskeleton formation and that that the present observations represent drug-induced exaggerations of a normal phenomenon.
Insights
Taxol treatment in regenerating rat sciatic nerves caused microtubules to form channels, sequestering mitochondria and other organelles. These drug-induced structures may reveal normal mechanisms of organelle transport during nerve repair.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Axonal regeneration is crucial for nerve repair.
- Microtubules are key components of the axonal cytoskeleton, essential for transport and structure.
- Mitochondria are vital organelles for cellular energy supply, particularly important in energy-demanding processes like axonal regrowth.
Purpose of the Study:
- To investigate the ultrastructural effects of taxol on regenerating rat sciatic nerves.
- To examine the relationship between microtubules and axoplasmic organelles, especially mitochondria, during nerve regeneration.
- To understand the potential role of taxol-induced microtubule structures in organelle trafficking.
Main Methods:
- Ultrastructural examination using electron microscopy of rat sciatic nerves.
- Local injection of taxol, a microtubule assembly-promoting compound.
- Analysis of microtubule organization and association with axoplasmic organelles within regenerating axons.
Main Results:
- Prodigious accumulation of axonal microtubules was observed.
- Microtubules formed multilayered channels sequestering axoplasmic organelles, including mitochondria.
- A 5 nm filament, possibly from microtubule side-arm material, was found between microtubule layers.
- Intermediate filaments appeared later within these microtubule channels.
Conclusions:
- Taxol treatment leads to drug-induced exaggerations of normal microtubule-organelle associations.
- These microtubule channels may play a role in mitochondrial transport across the lesion site.
- Taxol might impede axonal regrowth by affecting early cytoskeleton formation.