Open Access Repository

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


Downloads per month over past year

King, AE, Dickson, TC, Blizzard, CA, Foster, SS, Chung, RS, West, AK, 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, vol. 26, no. 8 , pp. 2151-2159 , doi: 10.1111/j.1460-9568.2007.05845.x.

[img] PDF
King_Euro_J_Neu...pdf | Request a copy
Full text restricted


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
Authors/Creators:King, AE and Dickson, TC and Blizzard, CA and Foster, SS and Chung, RS and West, AK and Chuah, MI and Vickers, JC
Journal or Publication Title: European Journal of Neuroscience
ISSN: 0953-816X
DOI / ID Number: 10.1111/j.1460-9568.2007.05845.x
Additional Information:

The original publication is available at

Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page