Cuprizone
目录号 : GC68193Bis(cyclohexanone) Oxalyldihydrazone 是一种铜螯合剂，可与铜 (II) 形成深蓝色铜酮络合物。 铜酮反应可用于比色测试中是否存在痕量铜。Bis(cyclohexanone) Oxalyldihydrazone 可用于诱导小鼠的一些精神分裂症样行为。 Bis(cyclohexanone) Oxalyldihydrazone 作用于铜酶，包括 SOD1、细胞色素氧化酶和 DβH，从而导致氧化应激并增加某些大脑区域如内侧前额叶皮层 (PFC) 的 DA 水平[1]<
Cas No.:370-81-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bis(cyclohexanone) Oxalyldihydrazone, a copper chelator, can be used to coordinate Copper(II) to form an intensely coloured blue copper-cuprizone complex. The cuprizone reaction has been employed in colourimetric tests for the presence of trace lev
Cuprizone (0.5 mg/100 mg of diet and water given ad lib; p.o.) produces severe status spongious in the CNS, most prominently in the brain stem and cerebellar white matter of mice[1].
[1]. Suzuki K, et al. Status spongiosus of CNS and hepatic changes induced by cuprizone (biscyclohexanone oxalyldihydrazone). Am J Pathol. 1969 Feb;54(2):307-25.
[2]. Sanadgol N, et al. Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation. Metab Brain Dis. 2018 Feb;33(1):27-37.
[3]. M Jake Pushie, et al. Synthesis and structural characterization of copper-cuprizone complexes. Dalton Trans. 2022 Jun 29.
[4]. Haiyun Xu, et al. Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics. Front Behav Neurosci. 2010 Mar 18;4:8.
| Cas No. | 370-81-0 | SDF | Download SDF |
| 分子式 | C14H22N4O2 | 分子量 | 278.35 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5926 mL | 17.963 mL | 35.926 mL |
| 5 mM | 0.7185 mL | 3.5926 mL | 7.1852 mL |
| 10 mM | 0.3593 mL | 1.7963 mL | 3.5926 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The Cuprizone model for demyelination
Acta Neurol Scand Suppl 2008;188:72-6.PMID:18439226DOI:10.1111/j.1600-0404.2008.01036.x.
Background: Important advances in multiple sclerosis (MS) research have been made as a direct or indirect result of experiments in animal models for the disease, although MS is a disease only affecting humans. The Cuprizone model is a model for toxic demyelination. In this model, young mice are fed with the copper chelator Cuprizone, leading to oligodendrocyte death and a subsequent reversible demyelination. Spontaneous remyelination can be seen as early as 4 days after withdrawal of Cuprizone. Materials and methods: This article reviews previous research on this model and discusses the potential of the model for future application in MS research. Discussion: The Cuprizone model correlates with newer histopathological data in MS and is a valuable tool for studies on de- and remyelination. The use of the C57BL/6 strain offers the potential for future studies on transgene and knockout mice.
Ferroptosis Mediates Cuprizone-Induced Loss of Oligodendrocytes and Demyelination
J Neurosci 2020 Nov 25;40(48):9327-9341.PMID:33106352DOI:10.1523/JNEUROSCI.1749-20.2020.
Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. Cuprizone (CZ), a copper chelator, is widely used to study demyelination and remyelination in the CNS, in the context of MS. However, the mechanisms underlying oligodendrocyte (OL) cell loss and demyelination are not known. As copper-containing enzymes play important roles in iron homeostasis and controlling oxidative stress, we examined whether chelating copper leads to disruption of molecules involved in iron homeostasis that can trigger iron-mediated OL loss. We show that giving mice (male) CZ in the diet induces rapid loss of OL in the corpus callosum by 2 d, accompanied by expression of several markers for ferroptosis, a relatively newly described form of iron-mediated cell death. In ferroptosis, iron-mediated free radicals trigger lipid peroxidation under conditions of glutathione insufficiency, and a reduced capacity to repair lipid damage. This was further confirmed using a small-molecule inhibitor of ferroptosis that prevents CZ-induced loss of OL and demyelination, providing clear evidence of a copper-iron connection in CZ-induced neurotoxicity. This work has wider implications for disorders, such as multiple sclerosis and CNS injury.SIGNIFICANCE STATEMENT Cuprizone (CZ) is a copper chelator that induces demyelination. Although it is a widely used model to study demyelination and remyelination in the context of multiple sclerosis, the mechanisms mediating demyelination is not fully understood. This study shows, for the first time, that CZ induces demyelination via ferroptosis-mediated rapid loss of oligodendrocytes. This work shows that chelating copper with CZ leads to the expression of molecules that rapidly mobilize iron from ferritin (an iron storage protein), that triggers iron-mediated lipid peroxidation and oligodendrocyte loss (via ferroptosis). Such rapid mobilization of iron from cellular stores may also play a role in cell death in other neurologic conditions.
Oligodendrocyte death and myelin loss in the Cuprizone model: an updated overview of the intrinsic and extrinsic causes of Cuprizone demyelination
Mol Neurodegener 2022 May 7;17(1):34.PMID:35526004DOI:10.1186/s13024-022-00538-8.
The dietary consumption of Cuprizone - a copper chelator - has long been known to induce demyelination of specific brain structures and is widely used as model of multiple sclerosis. Despite the extensive use of Cuprizone, the mechanism by which it induces demyelination are still unknown. With this review we provide an updated understanding of this model, by showcasing two distinct yet overlapping modes of action for cuprizone-induced demyelination; 1) damage originating from within the oligodendrocyte, caused by mitochondrial dysfunction or reduced myelin protein synthesis. We term this mode of action 'intrinsic cell damage'. And 2) damage to the oligodendrocyte exerted by inflammatory molecules, brain resident cells, such as oligodendrocytes, astrocytes, and microglia or peripheral immune cells - neutrophils or T-cells. We term this mode of action 'extrinsic cellular damage'. Lastly, we summarize recent developments in research on different forms of cell death induced by Cuprizone, which could add valuable insights into the mechanisms of Cuprizone toxicity. With this review we hope to provide a modern understanding of cuprizone-induced demyelination to understand the causes behind the demyelination in MS.
The Cuprizone Model: Dos and Do Nots
Cells 2020 Mar 31;9(4):843.PMID:32244377DOI:10.3390/cells9040843.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of the disease are available to study MS pathogenesis and to develop new therapeutic options. During the last decade, the model of toxic demyelination induced by Cuprizone has become more and more popular, and it has contributed substantially to our understanding of distinct yet important aspects of the MS pathology. Here, we aim to provide a practical guide on how to use the Cuprizone model and which pitfalls should be avoided.
The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the Cuprizone model of multiple sclerosis
Glia 2022 Jul;70(7):1215-1250.PMID:35107839DOI:10.1002/glia.24148.
In human demyelinating diseases such as multiple sclerosis (MS), an imbalance between demyelination and remyelination can trigger progressive degenerative processes. The clearance of myelin debris (phagocytosis) from the site of demyelination by microglia is critically important to achieve adequate remyelination and to slow the progression of the disease. However, how microglia phagocytose the myelin debris, and why clearance is impaired in MS, is not fully known; likewise, the role of the microglia in remyelination remains unclear. Recent studies using Cuprizone (CPZ) as an animal model of central nervous system demyelination revealed that the up-regulation of signaling proteins in microglia facilitates effective phagocytosis of myelin debris. Moreover, during demyelination, protective mediators are released from activated microglia, resulting in the acceleration of remyelination in the CPZ model. In contrast, inadequate microglial activation or recruitment to the site of demyelination, and the production of toxic mediators, impairs remyelination resulting in progressive demyelination. In addition to the microglia-mediated phagocytosis, astrocytes play an important role in the phagocytic process by recruiting microglia to the site of demyelination and producing regenerative mediators. The current review is an update of these emerging findings from the CPZ animal model, discussing the roles of microglia and astrocytes in phagocytosis and myelination.