Changes of hippocampal Cu/Zn-superoxide dismutase after kainate treatment in the rat.
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.
Kim
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Section of Pharmacology, Department of Pharmacy, College of Pharmacy, Kangwon National University, Chunchon, South Korea. kimhc@cc.kangwon.ac.kr
Bing
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Jhoo
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Ko
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Kim
W K
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Suh
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Kim
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Kato
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Hong
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D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology; D015152:Blotting, Northern; D004789:Enzyme Activation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D037102:Lectins / Q000493:pharmacokinetics; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D012333:RNA, Messenger; D009418:S100 Proteins; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D007608:Kainic Acid