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dc.contributor.authorRainey-Smith, S.R.*
dc.contributor.authorAndersson, D.A.*
dc.contributor.authorWilliams, R.J.*
dc.contributor.authorRattray, Marcus*
dc.date.accessioned2014-04-28T11:14:25Z
dc.date.available2014-04-28T11:14:25Z
dc.date.issued2010
dc.identifier.citationRainey-Smith, S. R., Andersson, D. A., Williams, R. J., Rattray, M. (2010) Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration. Journal of Neurochemistry, 113(3), 692-703.
dc.identifier.urihttp://hdl.handle.net/10454/6147
dc.descriptionNo
dc.description.abstractThe alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNFalpha) have both been implicated in motor neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease. TNFalpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNFalpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/mL, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using fura-2-acetoxymethyl ester microfluorimetry, we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggest that TNFalpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in amyotrophic lateral sclerosis.
dc.language.isoen
dc.subjectAnimals
dc.subjectBiotinylation
dc.subjectBlotting
dc.subjectWestern
dc.subjectCalcium
dc.subjectMetabolism
dc.subjectCalcium signaling
dc.subjectDrug effects
dc.subjectCell survival
dc.subjectDrug effects
dc.subjectCells
dc.subjectCultured
dc.subjectExcitatory amino acid agonists
dc.subjectToxicity
dc.subjectFemale
dc.subjectFluorescent antibody technique
dc.subjectKainic acid
dc.subjectAntagonists & inhibitors
dc.subjectToxicity
dc.subjectMice
dc.subjectMotor neurons
dc.subjectDrug effects
dc.subjectNerve degeneration
dc.subjectPathology
dc.subjectNeuroprotective agents
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectPregnancy
dc.subjectReceptors
dc.subjectAMPA
dc.subjectAntagonists & inhibitors
dc.subjectBiosynthesis
dc.subjectGenetics
dc.subjectReceptors
dc.subjectCell surface
dc.subjectBiosynthesis
dc.subjectReceptors
dc.subjectTumor necrosis factor
dc.subjectDrug effects
dc.subjectReverse transcriptase polymerase chain reaction
dc.subjectSpectrometry
dc.subjectFluorescence
dc.subjectTumor necrosis factor-alpha
dc.subjectPharmacology
dc.subjectp38 mitogen-activated protein kinases
dc.subjectREF 2014
dc.titleTumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration
dc.typeArticle
dc.type.versionNo full-text in the repository
dc.identifier.doihttps://doi.org/10.1111/j.1471-4159.2010.06634.x
dc.openaccess.statusclosedAccess


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