Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice
| Autor: | Jung Jin Hwang, Jin-Hee Shin, Tae-Youn Kim, Joo-Yong Lee, Jean Kim, Jae-Young Koh, Byung Joo Gwag |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Transgene Excitotoxicity chemistry.chemical_element Mice Transgenic Endogeny Zinc medicine.disease_cause lcsh:RC321-571 Mice Superoxide Dismutase-1 Internal medicine medicine Animals Homeostasis Amyotrophic lateral sclerosis lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Chelating Agents Motor Neurons Aldehydes Mutation Superoxide Dismutase Chemistry Amyotrophic Lateral Sclerosis medicine.disease Zinc chelator Up-Regulation Motoneurons Survival Rate Disease Models Animal Oxidative Stress HNE Endocrinology Spinal Cord Neurology Astrocytes Nerve Degeneration ALS Neuroscience Oxidative stress |
| Zdroj: | Neurobiology of Disease, Vol 34, Iss 2, Pp 221-229 (2009) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2009.01.004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect