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
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Dietary Iron
Parkinson Disease
Iron
Corpus Striatum
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine
Iron Chelating Agents
Sphingomyelins
Dopaminergic Neurons
Apoptosis

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

Role of dietary iron restriction in a mouse model of Parkinson's disease. / Levenson, Cathy W.; Cutler, Roy G.; Ladenheim, Bruce; Cadet, Jean L.; Hare, Joan; Mattson, Mark P.

In: Experimental Neurology, Vol. 190, No. 2, 12.2004, p. 506-514.

Research output: Contribution to journalArticle

Levenson, CW, Cutler, RG, Ladenheim, B, Cadet, JL, Hare, J & Mattson, MP 2004, 'Role of dietary iron restriction in a mouse model of Parkinson's disease', Experimental Neurology, vol. 190, no. 2, pp. 506-514. https://doi.org/10.1016/j.expneurol.2004.08.014
Levenson CW, Cutler RG, Ladenheim B, Cadet JL, Hare J, Mattson MP. Role of dietary iron restriction in a mouse model of Parkinson's disease. Experimental Neurology. 2004 Dec;190(2):506-514. https://doi.org/10.1016/j.expneurol.2004.08.014
Levenson, Cathy W. ; Cutler, Roy G. ; Ladenheim, Bruce ; Cadet, Jean L. ; Hare, Joan ; Mattson, Mark P. / Role of dietary iron restriction in a mouse model of Parkinson's disease. In: Experimental Neurology. 2004 ; Vol. 190, No. 2. pp. 506-514.
@article{2168558d5569469d98ff15e9178b8e8d,
title = "Role of dietary iron restriction in a mouse model of Parkinson's disease",
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.",
keywords = "Apoptosis, Desferrioxiamine, Iron deficiency, MPTP, p53, Parkinson's disease, Striatum",
author = "Levenson, {Cathy W.} and Cutler, {Roy G.} and Bruce Ladenheim and Cadet, {Jean L.} and Joan Hare and Mattson, {Mark P.}",
year = "2004",
month = "12",
doi = "10.1016/j.expneurol.2004.08.014",
language = "English (US)",
volume = "190",
pages = "506--514",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Role of dietary iron restriction in a mouse model of Parkinson's disease

AU - Levenson, Cathy W.

AU - Cutler, Roy G.

AU - Ladenheim, Bruce

AU - Cadet, Jean L.

AU - Hare, Joan

AU - Mattson, Mark P.

PY - 2004/12

Y1 - 2004/12

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Desferrioxiamine

KW - Iron deficiency

KW - MPTP

KW - p53

KW - Parkinson's disease

KW - Striatum

UR - http://www.scopus.com/inward/record.url?scp=8644283779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8644283779&partnerID=8YFLogxK

U2 - 10.1016/j.expneurol.2004.08.014

DO - 10.1016/j.expneurol.2004.08.014

M3 - Article

C2 - 15530889

AN - SCOPUS:8644283779

VL - 190

SP - 506

EP - 514

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 2

ER -