Intranigral iron infusion in rats: A progressive model for excess nigral iron levels in Parkinson’s disease?
Increased iron levels are present within the substantia nigra zona compacta (SNc) of Parkinson’s-diseased (PD) brains. Neurodegeneration within the SNc may be a direct consequence of increased iron because of iron’s ability to catalyze cytotoxic free radical formation. We have developed an animal model based on excess nigral iron in PD through intranigral infusion of iron citrate in rats. These infusions cause a long-term and dose-related increase in nigral iron, with accompanying dose-related neuronal loss/gliosis within SNc and associated decreases in striatal dopaminergic markers. Moreover, intranigral iron infusion provides several long-term “progressive” changes including: 1) a progressive decrease in striatal dopamine and HVA, 2) a progressive atrophy of the substantia nigra, and 3) a progressive increase in apomorphine-induced rotational behavior. Since nigral lipid peroxidation is elevated following nigral iron infusion, free radical formation and ensuing oxidative damage may be involved in iron’s neurotoxicity within the substantia nigra. This intranigral iron infusion model could be of extraordinary value in testing antioxidants for treating/preventing PD.
KeywordsIron Infusion Iron Staining Iron Citrate Parkinsonian Brain Extensive Neuronal Loss
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