Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment

Hyoung Chun Kim, Guoying Bing, Wang Kee Jhoo, Won Ki Kim, Eun Joo Shin, Eon Sup Park, Yong Soon Choi, Dong Wook Lee, Chan Young Shin, Jae Ryun Ryu, Kwang Ho Ko

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

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 languageEnglish
Pages (from-to)211-220
Number of pages10
JournalBehavioural Brain Research
Volume131
Issue number1-2
DOIs
Publication statusPublished - 2002 Apr 11
Externally publishedYes

Keywords

  • Hippocampus
  • Kainic acid
  • Lipofuscin
  • Oxidative stress
  • Seizures
  • Senescence-accelerated mouse

ASJC Scopus subject areas

  • Behavioral Neuroscience

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