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
Copyright policy )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
J. Neurochem.(2010)113, 692–703.AbstractThe α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNFα) have both been implicated in motor neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease. TNFα 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 TNFα receptor activation, GluR2 availability, AMPAR‐mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFα (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 TNFα 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 TNFα acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in amyotrophic lateral sclerosis.
- University of Reading United Kingdom
- Wolfson Centre for Age-Related Diseases United Kingdom
- Kings College London, University of London United Kingdom
- King's College London United Kingdom
- Murdoch University Australia
Fluorescent Antibody Technique, Cell survival, Receptors, Tumor Necrosis Factor, Mice, Phosphatidylinositol 3-Kinases, Pregnancy, Receptors, AMPA, Pathology, Excitatory Amino Acid Agonists, Tumor necrosis factor-alpha, REF 2014, Reverse transcriptase polymerase chain reaction, Cells, Cultured, Motor neurons, Motor Neurons, Cultured, Kainic Acid, Blotting, Fluorescent antibody technique, Neuroprotective Agents, Kainic acid, Female, Western, 570, Tumor necrosis factor, Cell Survival, Cells, Antagonists & inhibitors, Blotting, Western, 610, Excitatory amino acid agonists, Receptors, Cell Surface, Biosynthesis, Cell surface, Fluorescence, Neuroprotective agents, Genetics, Animals, Biotinylation, Calcium Signaling, Receptors, AMPA, Nerve degeneration, p38 mitogen-activated protein kinases, Pharmacology, Drug effects, Toxicity, Spectrometry, Calcium signaling, Metabolism, Nerve Degeneration, Calcium
Fluorescent Antibody Technique, Cell survival, Receptors, Tumor Necrosis Factor, Mice, Phosphatidylinositol 3-Kinases, Pregnancy, Receptors, AMPA, Pathology, Excitatory Amino Acid Agonists, Tumor necrosis factor-alpha, REF 2014, Reverse transcriptase polymerase chain reaction, Cells, Cultured, Motor neurons, Motor Neurons, Cultured, Kainic Acid, Blotting, Fluorescent antibody technique, Neuroprotective Agents, Kainic acid, Female, Western, 570, Tumor necrosis factor, Cell Survival, Cells, Antagonists & inhibitors, Blotting, Western, 610, Excitatory amino acid agonists, Receptors, Cell Surface, Biosynthesis, Cell surface, Fluorescence, Neuroprotective agents, Genetics, Animals, Biotinylation, Calcium Signaling, Receptors, AMPA, Nerve degeneration, p38 mitogen-activated protein kinases, Pharmacology, Drug effects, Toxicity, Spectrometry, Calcium signaling, Metabolism, Nerve Degeneration, Calcium
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).25 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!