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

Edina Pandur, Ramóna Pap, Edit Varga, Gergely Jánosa, S. Komoly, Judit Fórizs, Katalin Sipos

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume20
Issue number9
DOIs
Publication statusPublished - May 7 2019

Fingerprint

Cuprizone
metabolism
Inbred C57BL Mouse
Metabolism
mice
Iron
iron
lipid metabolism
intoxication
liver
genes
Liver
homeostasis
Demyelinating Diseases
Genes
Corpus Callosum
Oligodendroglia
Lipid Metabolism
myelin
Multiple Sclerosis

Keywords

  • corpus callosum
  • cuprizone
  • hepcidin
  • iron metabolism
  • liver
  • multiple sclerosis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice. / Pandur, Edina; Pap, Ramóna; Varga, Edit; Jánosa, Gergely; Komoly, S.; Fórizs, Judit; Sipos, Katalin.

In: International journal of molecular sciences, Vol. 20, No. 9, 07.05.2019.

Research output: Contribution to journalArticle

Pandur, Edina ; Pap, Ramóna ; Varga, Edit ; Jánosa, Gergely ; Komoly, S. ; Fórizs, Judit ; Sipos, Katalin. / Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 9.
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