Cuprizone neurotoxicity, copper deficiency and neurodegeneration

被引：54

作者：

Benetti, Federico ^{[2
]}

Ventura, Marcello ^{[2
]}

Salmini, Benedetta ^{[2
]}

Ceola, Stefano ^{[3
]}

Carbonera, Donatella ^{[3
]}

Mammi, Stefano ^{[3
]}

Zitolo, Andrea ^{[4
]}

D'Angelo, Paola ^{[4
]}

Urso, Emanuela ^{[5
]}

Maffia, Michele ^{[5
]}

Salvato, Benedetto ^{[2
]}

Spisni, Enzo ^{[1
]}

机构：

[1] Univ Bologna, Dept Expt Biol, Bologna, Italy

[2] Univ Padua, Dept Biol, I-35121 Padua, Italy

[3] Univ Padua, Dept Chem Sci, I-35131 Padua, Italy

[4] Univ Roma La Sapienza, Dept Chem, I-00185 Rome, Italy

[5] Univ Salento, Dept Biol & Environm Sci & Technol, I-73100 Lecce, Italy

来源：

NEUROTOXICOLOGY | 2010年 / 31卷 / 05期

关键词：

Cuprizone; Copper deficiency; Ceruloplasmin activity; Neurodegeneration; BRAIN-BARRIER PERMEABILITY; MENKES-DISEASE; INDUCED DEMYELINATION; CANDIDATE GENE; MOUSE-BRAIN; CERULOPLASMIN; NEURONS; CELLS; REMYELINATION; ACTIVATION;

D O I：

10.1016/j.neuro.2010.05.008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：509 / 517

页数：9

共 49 条

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