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

7123 13 archive 355 disk0/00/00/71/23 2008-07-21 05:26:51 2008-07-21 05:26:51 2008-07-21 05:26:51 article show James.Vickers@utas.edu.au King AE A.E.King@utas.edu.au Dickson TC Tracey.Dickson@utas.edu.au Blizzard CA Catherine.Blizzard@utas.edu.au Foster SS Sandessa.Foster@utas.edu.au Chung RS Roger.Chung@utas.edu.au West AK awest@utas.edu.au Chuah MI Inn.Chuah@utas.edu.au Vickers JC James.Vickers@utas.edu.au Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons pub restricted The original publication is available at http://www.interscience.wiley.com/ category => A1 categoryDesc => Refereed Article in a Scholarly Journal eprintID => 0 field1 => European Journal of Neuroscience field10 => field11 => field12 => field13 => field2 => UK field3 => 26 field4 => 8 field5 => 2151-2159 field6 => Wiley-Blackwell Publishing Ltd. field7 => 0953-816X field8 => field9 => funding => S grant => lastUpdate => 12/03/2008 rfcd => 320704 seo => 730104 themeArea => PH title => Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons tor => SB uid => 50516 update => no 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. 2007 published European Journal of Neuroscience 26 8 2151-2159 10.1111/j.1460-9568.2007.05845.x TRUE 0953-816X http://dx.doi.org/10.1111/j.1460-9568.2007.05845.x 5925 3 7123 1 application/pdf en staffonly

King_Euro_J_Neurosci.pdf

King_Euro_J_Neurosci.pdf 845977 http://eprints.utas.edu.au/7123/1/King_Euro_J_Neurosci.pdf