Abstract:
: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 betaIII-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.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Chung RS,McCormack GH,King AE,West AK,Vickers JCdoi
10.1016/j.expneurol.2005.01.005keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
481-8issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(05)00009-9journal_volume
193pub_type
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