title: Effects of over- and under-expression of Cu,Zn-superoxide dismutase on the toxicity of glutamate analogs in transgenic mouse striatum.
abstract: Considerable evidence suggests that reactive oxygen species mediate the neurotoxic effects of ionotropic glutamate receptor activation. Accordingly, we have examined neuronal degeneration resulting from intrastriatal injection of quinolinic acid, an NMDA receptor agonist, and kainic acid in gene targeted and transgenic mice that under- or over-express copper, zinc superoxide dismutase (Cu,Zn-SOD; SOD-1). Elevated SOD-1 activity significantly protects against quinolinic acid and kainic acid neurotoxicity in the mouse striatum whereas reduced activity appears to potentiate neurotoxicity. Thus a 'gene-dose' effect of SOD-1 has been demonstrated with regard to excitotoxic mechanisms.
authors.affiliation: Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Charlestown 02129, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: A
authors.initials: A
authors.lastname: Reaume
authors.forename: R
authors.initials: R
authors.lastname: Scott
authors.forename: J T
authors.initials: JT
authors.lastname: Coyle
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D005971:Glutamates / Q000506:poisoning*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D005971:Glutamates; D012333:RNA, Messenger; D013482:Superoxide Dismutase