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 language | English (US) |
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Pages (from-to) | 506-514 |
Number of pages | 9 |
Journal | Experimental Neurology |
Volume | 190 |
Issue number | 2 |
DOIs | |
State | Published - Dec 2004 |
Externally published | Yes |
Keywords
- Apoptosis
- Desferrioxiamine
- Iron deficiency
- MPTP
- p53
- Parkinson's disease
- Striatum
ASJC Scopus subject areas
- Neurology
- General Neuroscience