Kainate-induced hippocampal DNA damage is attenuated in superoxide dismutase transgenic mice.
Peripheral administration of kainic acid (KA) can cause cell death in the hippocampus of rodents. This is thought to involve oxidative stress. In the present study, we tested the possibility that KA-induced neuronal cell death might be attenuated in CuZn superoxide dismutase transgenic (SOD-Tg) mice. Acute administration of KA causes animal death in a dose-dependent fashion; this was attenuated in SOD-Tg mice. Similarly, KA caused dose-dependent neuronal cell death in the hippocampus of wild-type mice; this cell death was attenuated in the SOD-Tg mice, in a gene-dosage-dependent fashion, with homozygous mice showing complete protection even at the highest dose (45 mg/kg) of KA used in this study. These results provide further support for the involvement of oxygen-based radicals in the toxic effects of KA.
Hirata
H
H
NIH/NIDA, Division of Intramural Research, Baltimore, MD 21224, USA.
Cadet
J L
JL
D000818:Animals; D017209:Apoptosis; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006579:Heterozygote; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006720:Homozygote; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D013482:Superoxide Dismutase; D007608:Kainic Acid