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Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons

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King, AE and Dickson, TC and Blizzard, CA and Foster, SS and Chung, RS and West, AK and Chuah, MI and Vickers, JC (2007) Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons. European Journal of Neuroscience, 26 (8). pp. 2151-2159. ISSN 0953-816X

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Abstract

Excitotoxicity has been implicated as a potential cause of neuronal degeneration in amyotrophic lateral sclerosis (ALS). It has not
been clear how excitotoxic injury leads to the hallmark pathological changes of ALS, such as the abnormal accumulation of
filamentous proteins in axons. We have investigated the effects of overactivation of excitatory receptors in rodent neurons maintained
in long-term culture. Excitotoxicity, mediated principally via non-N-methyl-d-aspartate (NMDA) receptors, caused axonal swelling and
accumulation of cytoskeletal proteins in the distal segments of the axons of cultured spinal, but not cortical, neurons. Axonopathy only
occurred in spinal neurons maintained for 3 weeks in vitro, indicating that susceptibility to axonal pathology may be related to relative
maturity of the neuron. Excitotoxic axonopathy was associated with the aberrant colocalization of phosphorylated and
dephosphorylated neurofilament proteins, indicating that disruption to the regulation of phosphorylation of neurofilaments may
lead to their abnormal accumulation. These data provide a strong link between excitotoxicity and the selective pattern of axonopathy
of lower motor neurons that underlies neuronal dysfunction in ALS.

Item Type: Article
Journal or Publication Title: European Journal of Neuroscience
Page Range: pp. 2151-2159
ISSN: 0953-816X
Identification Number - DOI: 10.1111/j.1460-9568.2007.05845.x
Additional Information:

The original publication is available at
http://www.interscience.wiley.com/

Date Deposited: 21 Jul 2008 05:26
Last Modified: 18 Nov 2014 03:46
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