title: Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment.
abstract: We have demonstrated that seizures induced by kainic acid (KA) are, at least in part, mediated via oxidative stress in rats [Life. Sci. 61 (1997) PL373; Brain Res. 853 (2000) 215; Brain Res. 874 (2000) 15; Neurosci. Lett. 281 (2000) 65]. In order to extend our findings, we employed the rodent aging model in this study. After KA treatments (once a day for 5 days; 20,20,20,20 and 40 mg/kg, i.p.), several parameters reflecting neurotoxic behaviors, oxidative stress [malondialdehyde (MDA) and protein carbonyl] and aging (lipofuscin-like substances) were compared between senile-prone (P8) and resistant (R1) strains of 9-month-old male senescence-accelerated mice (SAM). KA-induced neurotoxic signs as shown by mortality and seizure activity were more accentuated in the SAM-P8 than in the SAM-R1. Levels of MDA and carbonyl are consistently higher in the hippocampus of SAM-P8 than that of SAM-R1. Significant increases in the values of MDA and carbonyl were observed 4 h or 2 days after the final KA administration. This finding was more pronounced in the SAM-P8 than in the SAM-R1. Although a significant loss of hippocampal neurons was observed 7 days post-KA, at this time the MDA and carbonyl content had returned to near control levels. In contrast, fluorescent lipofuscin-like substances and lipofuscin granules were significantly increased 7 days after KA treatments. Therefore, our data suggests that mice in the senescence model are more susceptible to KA-induced seizures/oxidative damage, and that oxidative damage could be one of the casual factors in the accumulation of lipofuscin.
authors.affiliation: Neurotoxicology Program, Department of Pharmacy, College of Pharmacy, Kangwon National University, 200-701, Chunchon, South Korea. kimhc@cc.kangwon.ac.kr
authors.forename: Hyoung Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.forename: Wang Kee
authors.initials: WK
authors.lastname: Jhoo
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Shin
authors.forename: Eon Sup
authors.initials: ES
authors.lastname: Park
authors.forename: Yong Soon
authors.initials: YS
authors.lastname: Choi
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Lee
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Jae Ryun
authors.initials: JR
authors.lastname: Ryu
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002452:Cell Count; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008062:Lipofuscin / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000523:psychology; D018384:Oxidative Stress / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D008062:Lipofuscin; D009419:Nerve Tissue Proteins; D008315:Malondialdehyde; D007608:Kainic Acid