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

journal contribution
posted on 2023-05-16, 17:28 authored by Chung, RS, Graeme McCormackGraeme McCormack, Anna KingAnna King, Adrian WestAdrian West, James VickersJames Vickers
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.

History

Publication title

Experimental Neurology

Volume

193

Pagination

481-488

ISSN

0014-4886

Department/School

Tasmanian School of Medicine

Publisher

Elsevier Science

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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