title: Cellular and molecular neuropathology of the cuprizone mouse  model: clinical relevance for multiple sclerosis.
abstract: The cuprizone mouse model allows the investigation of the complex molecular mechanisms behind nonautoimmune-mediated demyelination and spontaneous remyelination. While it is generally accepted that oligodendrocytes are specifically vulnerable to cuprizone intoxication due to their high metabolic demands, a comprehensive overview of the etiology of cuprizone-induced pathology is still missing to date. In this review we extensively describe the physico-chemical mode of action of cuprizone and discuss the molecular and enzymatic mechanisms by which cuprizone induces metabolic stress, oligodendrocyte apoptosis, myelin degeneration and eventually axonal and neuronal pathology. In addition, we describe the dual effector function of the immune system which tightly controls demyelination by effective induction of oligodendrocyte apoptosis, but in contrast also paves the way for fast and efficient remyelination by the secretion of neurotrophic factors and the clearance of cellular and myelinic debris. Finally, we discuss the many clinical symptoms that can be observed following cuprizone treatment, and how these strengthened the cuprizone model as a useful tool to study human multiple sclerosis, schizophrenia and epilepsy.
authors.forename: Jelle
authors.initials: J
authors.lastname: Praet
authors.forename: Caroline
authors.initials: C
authors.lastname: Guglielmetti
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
authors.forename: Peter
authors.initials: P
authors.lastname: Ponsaerts
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003471:Cuprizone; D004195:Disease Models, Animal; D051379:Mice; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D003471:Cuprizone