Role of dietary iron restriction in a mouse model of Parkinson's disease

Cathy W. Levenson, Roy G. Cutler, Bruce Ladenheim, Jean L. Cadet, Joan Hare, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

There is a growing body of evidence suggesting that iron chelation may be a useful therapy in the treatment of Parkinson's Disease (PD). Experiments were designed to test the impact of dietary iron availability on the pathogenic process and functional outcome in a mouse model of PD. Mice were fed diets containing low (4 ppm) or adequate (48 ppm) amounts of iron for 6 weeks before the administration of MPTP, a mitochondrial toxin that damages nigrostriatal dopaminergic neurons and induces Parkinson-like symptoms. Low dietary iron increased serum total iron binding capacity (P <0.001). Consistent with neuronal protection, iron restriction increased sphingomyelin C16:0 and decreased ceramide C16:0. However, there was a 35% decrease in striatal dopamine (DA) in iron-restricted mice. Motor behavior was also impaired in these animals. In vitro studies suggested that severe iron restriction could lead to p53-mediated neuronal apoptosis. Administration of MPTP reduced striatal DA (P <0.01) and impaired motor behavior in iron-adequate mice. However, in iron-restricted mice, striatal dopamine levels and motor behavior were unchanged compared to saline-treated mice. Thus, while reduced iron may provide protection against PD-inducing insults such as MPTP, the role of iron in the synthesis of DA and neuronal survival should be considered, particularly in the development of iron-chelating agents to be used chronically in the clinical setting.

Original languageEnglish (US)
Pages (from-to)506-514
Number of pages9
JournalExperimental Neurology
Volume190
Issue number2
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

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Keywords

  • Apoptosis
  • Desferrioxiamine
  • Iron deficiency
  • MPTP
  • p53
  • Parkinson's disease
  • Striatum

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Levenson, C. W., Cutler, R. G., Ladenheim, B., Cadet, J. L., Hare, J., & Mattson, M. P. (2004). Role of dietary iron restriction in a mouse model of Parkinson's disease. Experimental Neurology, 190(2), 506-514. https://doi.org/10.1016/j.expneurol.2004.08.014