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Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice

One of the models to investigate the distinct mechanisms contributing to neurodegeneration in multiple sclerosis is based on cuprizone (CZ) intoxication. CZ is toxic to mature oligodendrocytes and produces demyelination within the central nervous system but does not cause direct neuronal damage. The...

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Autores principales: Pandur, Edina, Pap, Ramóna, Varga, Edit, Jánosa, Gergely, Komoly, Sámuel, Fórizs, Judit, Sipos, Katalin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539941/
https://www.ncbi.nlm.nih.gov/pubmed/31067791
http://dx.doi.org/10.3390/ijms20092257
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author Pandur, Edina
Pap, Ramóna
Varga, Edit
Jánosa, Gergely
Komoly, Sámuel
Fórizs, Judit
Sipos, Katalin
author_facet Pandur, Edina
Pap, Ramóna
Varga, Edit
Jánosa, Gergely
Komoly, Sámuel
Fórizs, Judit
Sipos, Katalin
author_sort Pandur, Edina
collection PubMed
description One of the models to investigate the distinct mechanisms contributing to neurodegeneration in multiple sclerosis is based on cuprizone (CZ) intoxication. CZ is toxic to mature oligodendrocytes and produces demyelination within the central nervous system but does not cause direct neuronal damage. The CZ model is suitable for better understanding the molecular mechanism of de- and remyelination processes of oligodendrocytes. CZ is a copper chelating agent and it also affects the iron metabolism in brain and liver tissues. To determine the early effect of CZ treatment on iron homeostasis regulation, cytosolic and mitochondrial iron storage, as well as some lipid metabolism genes, we investigated the expression of respective iron homeostasis and lipid metabolism genes of the corpus callosum (CC) and the liver after short-term CZ administration. In the present study C57BL/6 male mice aged four weeks were fed with standard rodent food premixed with 0.2 w/w% CZ for two or eight days. The major findings of our experiments are that short-term CZ treatment causes significant changes in iron metabolism regulation as well as in the expression of myelin and lipid synthesis-related genes, even before apparent demyelination occurs. Both in the CC and the liver the iron uptake, utilization and storage are modified, though not always the same way or to the same extent in the two organs. Understanding the role of iron in short-term and long-term CZ intoxication could provide a partial explanation of the discrepant signs of acute and chronic MS. These could contribute to understanding the development of multiple sclerosis and might provide a possible drug target.
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spelling pubmed-65399412019-06-04 Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice Pandur, Edina Pap, Ramóna Varga, Edit Jánosa, Gergely Komoly, Sámuel Fórizs, Judit Sipos, Katalin Int J Mol Sci Article One of the models to investigate the distinct mechanisms contributing to neurodegeneration in multiple sclerosis is based on cuprizone (CZ) intoxication. CZ is toxic to mature oligodendrocytes and produces demyelination within the central nervous system but does not cause direct neuronal damage. The CZ model is suitable for better understanding the molecular mechanism of de- and remyelination processes of oligodendrocytes. CZ is a copper chelating agent and it also affects the iron metabolism in brain and liver tissues. To determine the early effect of CZ treatment on iron homeostasis regulation, cytosolic and mitochondrial iron storage, as well as some lipid metabolism genes, we investigated the expression of respective iron homeostasis and lipid metabolism genes of the corpus callosum (CC) and the liver after short-term CZ administration. In the present study C57BL/6 male mice aged four weeks were fed with standard rodent food premixed with 0.2 w/w% CZ for two or eight days. The major findings of our experiments are that short-term CZ treatment causes significant changes in iron metabolism regulation as well as in the expression of myelin and lipid synthesis-related genes, even before apparent demyelination occurs. Both in the CC and the liver the iron uptake, utilization and storage are modified, though not always the same way or to the same extent in the two organs. Understanding the role of iron in short-term and long-term CZ intoxication could provide a partial explanation of the discrepant signs of acute and chronic MS. These could contribute to understanding the development of multiple sclerosis and might provide a possible drug target. MDPI 2019-05-07 /pmc/articles/PMC6539941/ /pubmed/31067791 http://dx.doi.org/10.3390/ijms20092257 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pandur, Edina
Pap, Ramóna
Varga, Edit
Jánosa, Gergely
Komoly, Sámuel
Fórizs, Judit
Sipos, Katalin
Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice
title Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice
title_full Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice
title_fullStr Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice
title_full_unstemmed Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice
title_short Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice
title_sort relationship of iron metabolism and short-term cuprizone treatment of c57bl/6 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539941/
https://www.ncbi.nlm.nih.gov/pubmed/31067791
http://dx.doi.org/10.3390/ijms20092257
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