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Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice.

Kim, TY | Hwang, JJ | Lee, JY | Shin, JH | Gwag, BJ  | Koh, JY
Neurobiology of disease, 34(2). : 221-229, 2009
Journal Title
Neurobiology of disease
Zinc dyshomeostasis may trigger oxidative stress, which is likely the key mechanism of neuronal death in amyotrophic lateral sclerosis (ALS), including familial forms such as G93A SOD-1 ALS. Since zinc binding by G93A SOD-1 is weaker than by normal SOD-1, we assessed whether labile zinc levels are altered in the spinal cords of G93A SOD-1 transgenic (Tg) mice. Whereas no zinc-containing cells were found in wild-type (WT) mice, neurons and astrocytes with high levels of labile zinc appeared in G93A SOD-1 Tg mice, in correlation with motoneuron degeneration. The level of HNE, an endogenous neurotoxic molecule, was increased around zinc-accumulating cells and mSOD-1 positive cells, suggesting a link between HNE, SOD-1 mutation and zinc accumulation. Moreover, exposure of cultured spinal neurons and astrocytes from G93A SOD-1 Tg mice to HNE increased labile zinc levels, and exposure to zinc increased 4-hydroxynonenal (HNE) levels, to a greater degree than in WT neurons and astrocytes. Administration of the zinc chelator TPEN extended survival in G93A SOD-1 Tg mice. These results indicate that zinc dyshomeostasis occurs in the spinal cords of Tg mice, and that this dyshomeostasis may contribute to motoneuron degeneration.

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Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
곽, 병주
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