These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.
Pubmed for Handhelds
PUBMED FOR HANDHELDS
Search MEDLINE/PubMed
Title: Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice. Author: Kim J, Kim TY, Hwang JJ, Lee JY, Shin JH, Gwag BJ, Koh JY. Journal: Neurobiol Dis; 2009 May; 34(2):221-9. PubMed ID: 19344646. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]