title: Cuprizone [bis(cyclohexylidenehydrazide)] is selectively toxic for mature oligodendrocytes.
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.
authors: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str-1, 30625 Hannover, Germany.
authors: Karelle
authors: K
authors: Bénardais
authors: Alexandra
authors: A
authors: Kotsiari
authors: Jelena
authors: J
authors: Skuljec
authors: Paraskevi N
authors: PN
authors: Koutsoudaki
authors: Viktoria
authors: V
authors: Gudi
authors: Vikramjeet
authors: V
authors: Singh
authors: Franca
authors: F
authors: Vulinović
authors: Thomas
authors: T
authors: Skripuletz
authors: Martin
authors: M
authors: Stangel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002614:Chelating Agents / Q000633:toxicity*; D003471:Cuprizone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002614:Chelating Agents; D003471:Cuprizone
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