title: A new model of cuprizone-mediated demyelination/remyelination.
abstract: In the central nervous system, demyelinating diseases, such as multiple sclerosis, result in devastating long-term neurologic damage, in part because of the lack of effective remyelination in the adult human brain. One model used to understand the mechanisms regulating remyelination is cuprizone-induced demyelination, which allows investigation of remyelination mechanisms in adult animals following toxin-induced demyelination. Unfortunately, the degree of demyelination in the cuprizone model can vary, which complicates understanding the process of remyelination. Previous work in our laboratory demonstrated that the Akt/mTOR pathway regulates active myelination. When given to young postnatal mice, the mTOR inhibitor, rapamycin, inhibits active myelination. In the current study, the cuprizone model was modified by the addition of rapamycin during cuprizone exposure. When administered together, cuprizone and rapamycin produced more complete demyelination and provided a longer time frame over which to investigate remyelination than treatment with cuprizone alone. The consistency in demyelination will allow a better understanding of the mechanisms initiating remyelination. Furthermore, the slower rate of remyelination provides a longer window of time in which to investigate the diverse contributing factors that regulate remyelination. This new model of cuprizone-induced demyelination could potentially aid in identification of new therapeutic targets to enhance remyelination in demyelinating diseases.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Hilary H
authors.initials: HH
authors.lastname: Sachs
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Bercury
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Popescu
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: S Priya
authors.initials: SP
authors.lastname: Narayanan
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA wendy.macklin@ucdenver.edu.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000633:toxicity; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000633:toxicity
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003471:Cuprizone; D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D008996:Monoamine Oxidase Inhibitors; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020123:Sirolimus; C512773:Olig2 protein, mouse
keywords: Akt; cuprizone; demyelination; mTOR; oligodendrocyte; rapamycin