89892 - King et al 2013.pdf (1.47 MB)
Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol
journal contribution
posted on 2023-05-17, 23:19 authored by Anna KingAnna King, Katherine SouthamKatherine Southam, Dittmann, J, James VickersJames VickersBACKGROUND: 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.
History
Publication title
Acta Neuropathologica CommunicationsArticle number
59Number
59Pagination
1-9ISSN
2051-5960Department/School
Wicking Dementia Research Education CentrePublisher
BioMed Central Ltd.Place of publication
United KingdomRights statement
Copyright the AuthorsRepository Status
- Open