Journal
BRAIN RESEARCH
Volume 964, Issue 1, Pages 100-106Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0006-8993(02)04083-0
Keywords
ganglioside; GT1b; kainic acid; melatonin; mitochondrial DNA; seizure; electrophoresis
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The effects of ganglioside GT1b or melatonin on damage to brain mitochondrial DNA (mtDNA) and seizures induced by kainic acid were investigated both in vivo and in vitro. An intraperitoneal (i.p.) injection of kainic acid (45 mg/kg) produced broad-spectrum limbic and severe sustained seizures in all of the treated mice. These seizures were completely abolished by an intracerebroventricular (i.c.v.) injection of ganglioside GT1b (90 nmol/brain), a potent inhibitor of glutamate receptor mediated activation and translocation of protein kinase C and lipid peroxidation, or an i.p. injection of melatonin (20 mg/kg), a potent scavenger of hydroxyl radicals (OH). The administration of kainic acid caused damage to mtDNA in brain frontal and central portion of cortex in mice. The damage to mtDNA was abolished by pre-injection of ganglioside GT1b (90 nmol/brain, i.c.v.) or melatonin (20 mg/kg, i.p.). In vitro exposure of kainic acid (0.25, 0.5 or 1.0 mM) inflicted damage to mtDNA in a concentration-dependent manner. The damage to mtDNA induced by 1.0 mM kainic acid was attenuated by the co-treatment with 60 muM ganglioside GT1b or 1.5 mM melatonin. Furthermore, kainic acid (0.5 or 1.0 mM) increased lipid peroxidation in a concentration-dependent manner when incubated with a homogenate prepared from mice brain at 37 degreesC for 20 or 60 min. However, the increased lipid peroxidation was completely abolished by the co-treatment with ganglioside GT1b (60 muM) or melatonin (1.5 mM). These results suggest that reactive oxygen species including hydroxyl radical (OH) may play a role in the damage to brain mtDNA and seizures induced by kainic acid. We conclude that the preventive effect of melatonin or ganglioside GT1b against kainic acid-induced mtDNA damage or seizures may be due to its scavenging of reactive oxygen species including the OH. (C) 2002 Elsevier Science B.V. All rights reserved.
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