Intranigral iron infusion in the rat. Acute elevations in nigral lipid peroxidation and striatal dopaminergic markers with ensuing nigral degeneration.
Iron is known to induce lipid peroxidation and recent evidence indicates that both iron and lipid peroxidation are elevated in the substantia nigra in Parkinson's disease (PD). To test whether excess intranigral iron induces lipid peroxidation, we infused an iron citrate solution (0.63 nmol in 0.25 microL) into the rat substantia nigra and measured nigral thiobarbituric acid reactive products at 1-h, 1-d, 1-wk, and 1-mo postinfusion. In a separate group of iron-infused animals, histologic analysis within the substantia nigra through 1-mo postinfusion was accomplished by thionine- and iron-staining, with concurrent assessment of striatal neurochemical markers. Concentrations of nigral thiobarbituric acid reactive products were significantly elevated at 1 h and 1 d in iron-infused animals compared to vehicle-infused and unoperated animals, with a return to control values by 1 wk. Similarly, striatal dopamine turnover was acutely elevated, suggesting damage to dopaminergic neurons, which was confirmed histologically. Although iron-staining within the iron diffusionary area was increased through the postinfusion month, there was an apparent progression of the cellular character of staining from predominantly neuronal to reactive glial and finally to oligodendroglial by 1 mo postinfusion. This progression of cellular iron-staining may indicate a shifting of infused iron to a more bound unreactive form, thus explaining only an acute elevation in lipid peroxidation through 1 d following intranigral iron infusion. The data indicate that damage to nigral neurons induced by iron infusion is transciently associated with a marker of oxidative damage and supports the possibility that iron-induced oxidative stress contributes to the pathogenesis of PD.
Sengstock
G J
GJ
Department of Biology, University of South Florida Tampa 33620, USA.
Zawia
N H
NH
Olanow
C W
CW
Dunn
A J
AJ
Arendash
G W
GW
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007501:Iron / Q000008:administration & dosage* / Q000494:pharmacology; D007502:Iron Chelating Agents; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001679:Biogenic Amines; D007502:Iron Chelating Agents; D017392:Thiobarbituric Acid Reactive Substances; D007501:Iron; D004298:Dopamine