Cuprizone Administration Alters the Iron Metabolism in the Mouse Model of Multiple Sclerosis.

Cellular and Molecular Neurobiology
E VargaK Sipos

Abstract

Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia. In the present study, we used the accepted experimental model of 0.2% CZ-containing diet with standard iron concentration to induce demyelination in the brain of C57BL/6 mice. Our aim was to examine the changes of iron homeostasis in the CC and as a part of the systemic iron regulation, in the liver. Our data showed that CZ treatment changed the iron metabolism of both tissues; however, it had more impact on the liver. Besides the alterations in the expressions of iron storage and import proteins, we detected reduced serum iron concentration and iron stores in the liver, together with elevated hepcidin levels and ...Continue Reading

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Citations

May 10, 2019·International Journal of Molecular Sciences·Edina PandurKatalin Sipos
Nov 15, 2019·Multiple Sclerosis Journal - Experimental, Translational and Clinical·Gabriel BstehThomas Berger
Aug 24, 2019·Neuroscience and Biobehavioral Reviews·Monokesh K SenPeter J Shortland
Oct 30, 2020·Frontiers in Immunology·Monokesh K SenDavid A Mahns

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
protein assay
electron microscopy

Software Mentioned

Matlab
Bio
Rad CFX Manager
ImageJ

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