Altered vulnerability to kainate excitotoxicity of transgenic-Cu/Zn SOD1 neurones.
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.
Spalloni
Alida
A
IRCCS Fondazione Santa Lucia Via Ardeatina 306 00179 Rome, Italy.
Pascucci
Tiziana
T
Albo
Federica
F
Ferrari
Francesca
F
Puglisi-Allegra
Stefano
S
Zona
Cristina
C
Bernardi
Giorgio
G
Longone
Patrizia
P
D000690:Amyotrophic Lateral Sclerosis; D000704:Analysis of Variance; D000818:Animals; D001216:Asparagine / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003035:Cobalt / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009543:Nifedipine / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology; D013482:Superoxide Dismutase / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D026941:Sodium Channel Blockers; D003035:Cobalt; D018698:Glutamic Acid; D013779:Tetrodotoxin; D001216:Asparagine; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D010751:Phosphopyruvate Hydratase; D009543:Nifedipine; D007608:Kainic Acid