Progressive changes in striatal dopaminergic markers, nigral volume, and rotational behavior following iron infusion...

Excess iron (Fe) within the substantia nigra zona compacta (SNc) has been implicated in the pathogenesis of Parkinson's disease (PD). We recently reported that intranigral Fe infusion into the rat substantia nigra (SN) induces dose-dependent SN neurodegeneration and associated reductions in striatal dopaminergic (DA) markers. The objective of the present study was to determine whether infused Fe is capable of inducing persistent/progressive neurodegenerative changes relevant to PD. Following unilateral infusions of vehicle, 1.25 or 2.10 nmol Fe into the rat SN, SNc neuronal loss, SN volume, striatal neurochemical markers, and apomorphine-induced rotational behavior were assessed at 2, 4, and 6 months. Semiquantitative analysis of thionine-stained SNc neurons demonstrated an initial modest neuronal loss which remained stable through 6 months postinfusion. Fe-induced SN atrophy was dose-dependent and progressive through 6 months. Striatal DA and homovanillic acid levels were progressively decreased at least through 4 months following 1.25 nmol Fe infusion; both doses of Fe induced significant reductions of both DA markers at 4 months with no recovery evident through 6 months. Apomorphine-induced rotational behavior progressively increased for both Fe infusion groups through the 6 months of testing. These data indicate that a single exposure of the SN to a modest amount of Fe can induce persistent/progressive changes occurring through a number of months postinfusion and further establishes intranigral Fe infusion as an animal model for PD.