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.
Original language | English |
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Pages (from-to) | 211-220 |
Number of pages | 10 |
Journal | Behavioural Brain Research |
Volume | 131 |
Issue number | 1-2 |
DOIs | |
State | Published - Apr 11 2002 |
Bibliographical note
Funding Information:This work was supported by the Brain Korea 21 project and a grant (#HMP-98-N-2-0013) from the Good Health Research and Development Project (1998) of the Ministry of Health and Welfare, Korea, and by the Institute of Pharmaceutical Science, Kangwon National University, Korea.
Keywords
- Hippocampus
- Kainic acid
- Lipofuscin
- Oxidative stress
- Seizures
- Senescence-accelerated mouse
ASJC Scopus subject areas
- Behavioral Neuroscience