DOI: 10.1007/s12640-017-9704-2 Pages: 570-577
Article Type: ORIGINAL ARTICLE

Investigation of Cuprizone Inactivation by Temperature

1. Hannover Medical School, Clinical Neuroimmunology and Neurochemistry, Department of Neurology

2. Center for Systems Neuroscience

3. Hannover Medical School, Institute for Laboratory Animal Science and Central Animal Facility

4. Hannover Medical School, Department of Neurology

Correspondence to:
Martin Stangel
Tel: +49 511 532 6676
Email: Stangel.Martin@mh-hannover.de

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Abstract

Animal models, such as cuprizone (bis-cyclohexanone oxaldihydrazone) feeding, are helpful to study experimental demyelination and remyelination in the context of diseases like multiple sclerosis. Cuprizone is a copper chelator, which when supplemented to the normal food of C57BL/6J mice in a concentration of 0.2% leads to oligodendroglial loss, subsequent microglia and astrocyte activation, resulting in demyelination. Termination of the cuprizone diet results in remyelination, promoted by newly formed mature oligodendrocytes. The exact mode of cuprizone’s action is not well understood, and information about its inactivation and cleavage are still not available. The knowledge of these processes could lead to a better understanding of cuprizone’s mode of action, as well as a safer handling of this toxin. We therefore performed experiments with the aim to inactivate cuprizone by thermal heating, since it was suggested in the past that cuprizone is heat sensitive. C57BL/6J mice were fed for 4 weeks with 0.2% cuprizone, either thermally pretreated (60, 80, 105, 121 °C) or not heated. In addition, primary rat oligodendrocytes, as a known selective toxic target of cuprizone, were incubated with 350 μM cuprizone solutions, which were either thermally pretreated or not. Our results demonstrate that none of the tested thermal pretreatment conditions could abrogate or restrict the toxic and demyelinating effects of cuprizone, neither in vitro nor in vivo. In conclusion, the current study rebuts the hypothesis of cuprizone as a heat-sensitive compound, as well as the assumption that heat exposure is a reason for an insufficient demyelination of cuprizone-containing pellets.

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  • Accepted: Jan 12, 2017
  • Online: Jan 26, 2017
  • Revised: Jan 11, 2017

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