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

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 Neurol

journal_title

Experimental neurology

authors

Chung RS,McCormack GH,King AE,West AK,Vickers JC

doi

10.1016/j.expneurol.2005.01.005

keywords:

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

481-8

issue

2

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(05)00009-9

journal_volume

193

pub_type

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