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PMID:10640619

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Citation

Kim, H, Bing, G, Jhoo, W, Ko, KH, Kim, WK, Suh, JH, Kim, SJ, Kato, K and Hong, JS (2000) Changes of hippocampal Cu/Zn-superoxide dismutase after kainate treatment in the rat. Brain Res. 853:215-26

Abstract

In order to evaluate the putative role of Cu,Zn-superoxide dismutase (SOD-1) in the antioxidant defense mechanism during the neurodegenerative process, we examined the level of mRNA, the specific activity and immunocytochemical distribution for SOD-1 in the rat hippocampus after systemic injection of kainic acid (KA). Hippocampal SOD-1 mRNA levels were significantly increased by the seizure intensity 3 and 7 days after KA. These enhanced mRNA levels for SOD-1 were consistent with the increased specific activities for SOD-1, suggesting that the superoxide radical generated in neurotoxic lesion, induced SOD-1 mRNA. The CA1 and CA3 neurons lost their SOD-1-like immunoreactivity, whereas SOD-1-positive glia-like cells mainly proliferated throughout the CA1 sector and had an intense immunoreactivity at 3 and 7 days after KA. This immunocytochemical distribution for SOD-1-positive non-neuronal elements was similar to that for glial fibrillary acidic protein (GFAP)-positive cells. Each immunoreactivity for SOD-1-positive non-neuronal cell or GFAP in the layers of CA1 and CA3 disappeared 3 and 7 days after a maximal stage 5 seizure. On the other hand, activated microglial cells as selectively marked with the lectin occurred in the areas affected by KA-induced lesion. Double-labeling immunocytochemical analysis demonstrated the co-localization of SOD-1-positive glia-like cells and reactive astrocytes as labeled by GFAP or S-100 protein immunoreactivity. This finding suggested that the mobilization of astroglial cells for the synthesis of SOD-1 protein is a response to the KA insult designed to decrease the neurotoxicity induced by oxygen-derived free radicals. Therefore, these alterations might reflect the regulatory role of SOD-1 against oxygen-derived free radical-induced neuronal degeneration after systemic KA administration.

Links

PubMed

Keywords

Animals; Astrocytes/cytology; Astrocytes/enzymology; Blotting, Northern; Enzyme Activation/drug effects; Glial Fibrillary Acidic Protein/biosynthesis; Hippocampus/cytology; Hippocampus/drug effects; Hippocampus/enzymology; Immunohistochemistry; Kainic Acid/pharmacology; Lectins/pharmacokinetics; Male; Microglia/metabolism; Neurons/cytology; Neurons/drug effects; Neurons/enzymology; RNA, Messenger/metabolism; Rats; Rats, Sprague-Dawley; S100 Proteins/biosynthesis; Superoxide Dismutase/metabolism

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