期刊
NEUROTOXICOLOGY
卷 31, 期 5, 页码 509-517出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2010.05.008
关键词
Cuprizone; Copper deficiency; Ceruloplasmin activity; Neurodegeneration
资金
- MIUR [FIRB 2003 RBNE03FMCJ]
Cuprizone is used to obtain demyelination in mice. Cuprizone-treated mice show symptoms similar to several neurodegenerative disorders such as severe status spongiosus. Although it has a simple chemical formula, its neurotoxic mechanism is still unknown. In this work, we examined both physico-chemical properties and biological effects of cuprizone. Our results indicate that cuprizone has very complicated and misunderstood solution chemistry. Moreover, we show here the inability of cuprizone to cross neither the intestinal epithelial barrier nor the neuronal cell membrane, as well its high tolerability by cultured neurons. If added to mice diet, cuprizone does not accumulate in liver or in brain. Therefore, its neurotoxic effect is explainable only in terms of its capability to chelate copper, leading to chronic copper deficiency. (C) 2010 Elsevier Inc. All rights reserved.
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