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Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol


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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DOI: doi:10.1186/2051-5960-1-59


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
Keywords:Excitotoxicity, Axon Degeneration, Alzheimer's disease, Taxol, Caspase
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
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:16
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2014-03-18
Last Modified:2017-12-08
Downloads:290 View Download Statistics

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