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Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol
Citation
King, AE and Southam, KA and Dittmann, J and Vickers, JC, Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol, Acta Neuropathologica Communications, 1 Article 59. ISSN 2051-5960 (2013) [Refereed Article]
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Copyright Statement
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Official URL: http://www.actaneurocomms.org/content/1/1/59
DOI: doi:10.1186/2051-5960-1-59
Abstract
BACKGROUND:
Axon degeneration, a key pathological event in many neurodegenerative diseases and injury, can be induced by somatodendritic excitotoxin exposure. It is currently unclear, however, whether excitotoxin-induced axon degeneration is mechanistically similar to Wallerian degeneration, which occurs following axon transection, but does not involve axonal caspase activation.
RESULTS:
We have used mouse primary cortical neurons at 9 days in vitro, in a compartmented culture model that allows separation of the axon from the soma, to examine the pathological cascade of excitotoxin-induced axon degeneration. Excitotoxicity induced by chronic exposure to kainic acid, resulted in axonal fragmentation, which was associated with activation of caspase-3 in the axonal compartment. To examine the role of microtubules in these events, the microtubule-stabilizing agent, taxol, was added to either the axonal or somatodendritic compartment. Our results demonstrated that microtubule stabilization of axons resulted in a significant reduction in the number of fragmented axons following excitotoxin exposure. Interestingly, taxol exposure to either the somatodendritic or axonal compartment resulted in reduced caspase-3 activation in axons, suggesting that caspase activation is a downstream event of microtubule destabilization and involves signalling from the cell soma.
CONCLUSION:
These data suggest that excitotoxin-induced axon degeneration shows some mechanistic differences to Wallerian degeneration, and that microtubule stabilization may assist in protecting nerve cells from excitotoxic effects.
Item Details
Item Type: | Refereed Article |
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Keywords: | Excitotoxicity, Axon Degeneration, Alzheimer's disease, Taxol, Caspase |
Research Division: | Medical and Health Sciences |
Research Group: | Neurosciences |
Research Field: | Cellular Nervous System |
Objective Division: | Health |
Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
Objective Field: | Nervous System and Disorders |
UTAS Author: | King, AE (Professor Anna King) |
UTAS Author: | Southam, KA (Dr Katherine Southam) |
UTAS Author: | Dittmann, J (Mr Justin Dittmann) |
UTAS Author: | Vickers, JC (Professor James Vickers) |
ID Code: | 89892 |
Year Published: | 2013 |
Web of Science® Times Cited: | 14 |
Deposited By: | Wicking Dementia Research and Education Centre |
Deposited On: | 2014-03-18 |
Last Modified: | 2017-12-08 |
Downloads: | 264 View Download Statistics |
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