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

Citation

King, AE and Dickson, TC and Blizzard, CA and Foster, SS and Chung, RS and West, AK and Chuah, MI and Vickers, JC, 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 (2007) [Refereed Article]

DOI: doi:10.1111/j.1460-9568.2007.05845.x

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. © The Authors (2007).

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:King, AE (Associate Professor Anna King)
Author:Dickson, TC (Associate Professor Tracey Dickson)
Author:Blizzard, CA (Dr Catherine Blizzard)
Author:Foster, SS (Miss Sandessa Foster)
Author:Chung, RS (Associate Professor Roger Chung)
Author:West, AK (Professor Adrian West)
Author:Chuah, MI (Dr Inn Chuah)
Author:Vickers, JC (Professor James Vickers)
ID Code:50516
Year Published:2007
Web of Science® Times Cited:21
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2009-08-25
Downloads:0

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