Abstract
The neurotoxicity of the AMPA/kainate receptor agonist kainate was investigated in motor and cortical neurones from mice over-expressing the wild-type and G93A mutant form of Cu/Zn superoxide dismutase (SOD1) human gene, a mouse model of familial amyotrophic lateral sclerosis. G93A mutant motor neurones were more vulnerable and wild-type SOD1 motor neurones were more resistant to kainate toxicity than were controls. Voltage-gated Na channels blockage prevented G93A mutant SOD1 motor neurone death. Cortical cultures exhibited fewer differences in their vulnerability to kainate toxicity. These results demonstrate that SOD1 over-expression selectively affects the sensitivity to kainate excitotoxicity of motor neurones but not neocortical neurones, and that wild-type SOD1 expression increases the resistance to excitotoxicity of motor neurones.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyotrophic Lateral Sclerosis
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Analysis of Variance
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Animals
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Asparagine / metabolism
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Calcium Channel Blockers / pharmacology
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Cell Count / methods
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Cell Survival / drug effects
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Cells, Cultured
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Cerebral Cortex / cytology*
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Cobalt / pharmacology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Interactions
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Embryo, Mammalian
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Female
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Glial Fibrillary Acidic Protein / metabolism
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Glutamic Acid / metabolism
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Immunohistochemistry / methods
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Kainic Acid / toxicity*
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Male
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Mice
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Mice, Transgenic
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Motor Neurons / drug effects*
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Neurotoxins / toxicity*
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Nifedipine / pharmacology
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Phosphopyruvate Hydratase / metabolism
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Sodium Channel Blockers / pharmacology
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Spinal Cord / cytology
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Superoxide Dismutase / genetics*
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Tetrodotoxin / pharmacology
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Time Factors
Substances
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Calcium Channel Blockers
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Glial Fibrillary Acidic Protein
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Neurotoxins
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Sodium Channel Blockers
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Cobalt
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Glutamic Acid
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Tetrodotoxin
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Asparagine
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SOD1 G93A protein
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Superoxide Dismutase
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Phosphopyruvate Hydratase
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Nifedipine
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Kainic Acid