title: Investigation of Cuprizone Inactivation by Temperature.
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.
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Heckers
authors.affiliation: Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Held
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kronenberg
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.affiliation: Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Bleich
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gudi
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany. Stangel.Martin@mh-hannover.de.|Center for Systems Neuroscience, Hannover, Germany. Stangel.Martin@mh-hannover.de.|Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. Stangel.Martin@mh-hannover.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000373:Agglutinins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006358:Hot Temperature; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000373:Agglutinins; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; C000613192:adenomatous polyposis coli protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; D003471:Cuprizone
keywords: Cuprizone; Inactivation; Oligodendrocytes; Temperature