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Glutamate induces rapid loss of axonal neurofilament proteins from cortical neurons in vitro


Chung, RS and McCormack, GH and King, AE and West, AK and Vickers, JC, Glutamate induces rapid loss of axonal neurofilament proteins from cortical neurons in vitro, Experimental Neurology, 193, (2) pp. 481-488. ISSN 0014-4886 (2005) [Refereed Article]

DOI: doi:10.1016/j.expneurol.2005.01.005


One of the primary hallmarks of glutamate excitotoxicity is degradation of the neuronal cytoskeleton. Using a tissue culture approach, we have investigated the relationship between excitotoxicity and cytoskeletal degradation within axons, with particular reference to the axon specific neurofilament proteins. Neurofilaments were rapidly lost from axons over a 24-h period in response to excitotoxic insult (as observed by immunocytochemistry and western blotting), while other axonal cytoskeletal markers (such as βIII-tubulin) remained intact. Treatment with kainic acid and NMDA, or complementary experiments using the pharmacological glutamate receptors blockers CNQX (kainate/AMPA receptor antagonist) and MK-801 (NMDA receptor antagonist), demonstrated that neurofilament degeneration was mediated primarily by NMDA receptor activity. This work suggests that excitotoxicity triggers a progressive pathway of cytoskeletal degeneration within axons, initially characterised by the loss of neurofilament proteins. © 2005 Elsevier Inc. All rights reserved.

Item Details

Item Type:Refereed Article
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:Chung, RS (Associate Professor Roger Chung)
UTAS Author:McCormack, GH (Mr Graeme McCormack)
UTAS Author:King, AE (Professor Anna King)
UTAS Author:West, AK (Professor Adrian West)
UTAS Author:Vickers, JC (Professor James Vickers)
ID Code:38056
Year Published:2005
Web of Science® Times Cited:35
Deposited By:Anatomy and Physiology
Deposited On:2005-08-01
Last Modified:2007-05-29

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