An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis
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ORIGINAL ARTICLE
An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis Melissa A. Partridge 1,2 & Sumana Gopinath 2,4 & Simon J. Myers 2,3 & Jens R Coorssen 1,2
Received: 15 March 2015 / Accepted: 28 May 2015 / Published online: 12 June 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract An initial proteomic analysis of the cuprizone mouse model to characterise the breadth of toxicity by assessing cortex, skeletal muscle, spleen and peripheral blood mononuclear cells. Cuprizone treated vs. control mice for an initial characterisation. Select tissues from each group were pooled, analysed in triplicate using two-dimensional gel electrophoresis (2DE) and deep imaging and altered protein species identified using liquid chromatography tandem mass spectrometry (LC/MS/MS). Forty-three proteins were found to be uniquely detectable or undetectable in the cuprizone treatment group across the tissues analysed. Protein species identified in the cortex may potentially be linked to axonal damage in this model, and those in the spleen and peripheral blood mononuclear cells to the minimal peripheral immune cell infiltration into the central nervous system during cuprizone mediated demyelination. Primary oligodendrocytosis has been observed in
type III lesions in multiple sclerosis. However, the underlying mechanisms are poorly understood. Cuprizone treatment results in oligodendrocyte apoptosis and secondary demyelination. This initial analysis identified proteins likely related to axonal damage; these may link primary oligodendrocytosis and secondary axonal damage. Furthermore, this appears to be the first study of the cuprizone model to also identify alterations in the proteomes of skeletal muscle, spleen and peripheral blood mononuclear cells. Notably, protein disulphide isomerase was not detected in the cuprizone cohort; its absence has been linked to reduced major histocompatibility class I assembly and reduced antigen presentation. Overall, the results suggest that, like experimental autoimmune encephalomyelitis, results from the standard cuprizone model should be carefully considered relative to clinical multiple sclerosis. Keywords Autoimmunity . Multiple sclerosis . Neurodegeneration . Oligodendrocytosis
* Jens R Coorssen [email protected] Melissa A. Partridge [email protected] Sumana Gopinath [email protected] Simon J. Myers [email protected] 1
Department of Molecular Physiology, School of Medicine, University of Western Sydney, Penrith, NSW, Australia
2
Molecular Medicine Research Group, School of Medicine, University of Western Sydney, Penrith, NSW, Australia
3
Neuro-Cell Biology Laboratory, School of Science and Health, University of Western Sydney, Penrith, NSW, Australia
4
Department of Neurology, Campbelltown Hospital, Campbelltown, NSW, Australia
Abbreviations 2DE Two-dimensional gel electrophoresis AD Alzheimer’s disease AFD Automated frozen disruption CC Corpus callosum cCBB Colloidal Coomassie Brilliant Blue EAE Experimental autoimmune
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