Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment.
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.
Kim
Hyoung Chun
HC
Neurotoxicology Program, Department of Pharmacy, College of Pharmacy, Kangwon National University, 200-701, Chunchon, South Korea. kimhc@cc.kangwon.ac.kr
Bing
Guoying
G
Jhoo
Wang Kee
WK
Kim
Won Ki
WK
Shin
Eun Joo
EJ
Park
Eon Sup
ES
Choi
Yong Soon
YS
Lee
Dong Wook
DW
Shin
Chan Young
CY
Ryu
Jae Ryun
JR
Ko
Kwang Ho
KH
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
D018690:Excitatory Amino Acid Agonists; D008062:Lipofuscin; D009419:Nerve Tissue Proteins; D008315:Malondialdehyde; D007608:Kainic Acid