title: Proteomic analysis of demyelinated and remyelinating brain tissue following dietary cuprizone administration.
abstract: Cuprizone intoxication is a commonly used model of demyelination that allows the temporal separation of demyelination and remyelination. The underlying biochemical alterations leading to demyelination, using this model, remain unclear and may be multifold. Analysis of proteomic changes within the brains of cuprizone-exposed animals may help elucidate key cellular processes. In the current study, we report the results of the liquid chromatography tandem mass spectrometry analysis of total protein from the brain hemispheres of control and toxin-exposed mice at 6 weeks of exposure and after 3 and 6 weeks of recovery to identify protein changes during the remyelination phase. We found that at 6 weeks of cuprizone exposure, myelin proteins were reduced compared to controls and increased throughout the course of recovery, as expected. In contrast, other protein groups, such as proteins related to mitochondrial function, were increased at 6 weeks of treatment compared to untreated controls and returned toward control levels following withdrawal of toxin. These results suggest that a global proteomic analysis of the brain tissue of cuprizone-treated mice can identify changes related to the demyelination/remyelination process.
authors.affiliation: Biotechnology Discovery Research, Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. sean.werner@cookmedical.com
authors.forename: Sean R
authors.initials: SR
authors.lastname: Werner
authors.forename: Joy K
authors.initials: JK
authors.lastname: Saha
authors.forename: Carol L
authors.initials: CL
authors.lastname: Broderick
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Zhen
authors.forename: Richard E
authors.initials: RE
authors.lastname: Higgs
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Duffin
authors.forename: Rosamund C
authors.initials: RC
authors.lastname: Smith
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005526:Food, Formulated / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D040901:Proteomics / Q000379:methods*; D020127:Recovery of Function / Q000502:physiology
chemical_list: D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D003471:Cuprizone
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