Cuprizone [Bis(Cyclohexylidenehydrazide)] is Selectively Toxic for Mature Oligodendrocytes |
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Authors: | Karelle Bénardais Alexandra Kotsiari Jelena ?kuljec Paraskevi N Koutsoudaki Viktoria Gudi Vikramjeet Singh Franca Vulinovi? Thomas Skripuletz Martin Stangel |
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Institution: | 1. Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625, Hannover, Germany 2. Centre for Systems Neuroscience, Hannover, Germany 3. Department of Molecular Psychiatry, Hannover Medical School, Hannover, Germany 4. Department of Paediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany 5. Cellular and Molecular Neurobiology Laboratory, Hellenic Pasteur Institute Athens, Athens, Greece 6. Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Lübeck, Germany
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Abstract: | Cuprizone bis(cyclohexylidenehydrazide)]-induced toxic demyelination is an experimental animal model commonly used to study de- and remyelination in the central nervous system. In this model, mice are fed with the copper chelator cuprizone which leads to oligodendrocyte death with subsequent demyelination. The underlying mechanisms of cuprizone-induced oligodendrocyte death are still unknown, and appropriate in vitro investigations to study these mechanisms are not available. Thus, we studied cuprizone effects on rat primary glial cell cultures and on the neuroblastoma cell line SH-SY5Y. Treatment of cells with different concentrations of cuprizone failed to show effects on the proliferation and survival of SH-SY5Y cells, microglia, astrocytes, and oligodendrocyte precursor cells (OPC). In contrast, differentiated mature oligodendrocytes (OL) were found to be significantly affected by cuprizone treatment. This was accompanied by a reduced mitochondrial potential in cuprizone-treated OL. These results demonstrate that the main toxic target for cuprizone is mature OL, whilst other glial cells including OPC are not or only marginally affected. This explains the selective demyelination induced by cuprizone in vivo. |
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