Alteration of nigral iron and ferritin in 6-hydroxydopamine rat parkinsonian model

ABSTRACT

Iron-induced oxidative stress has been emphasized in the pathomechanism of Parkinson's disease (PD). Studies on the distribution of iron in the parkinsonian postmortem brain have demonstrated that iron deposition is selectively increased in substantia nigra pars compacta (SNc). This study was done to examine the alteration of nigral iron and ferritin in an animal model of parkinsonism and to understand the role of disturbed iron metabolism as a cause of PD. Hemiparkinsonian model was made by stereotaxically injecting 6-OHDA into the SN of Sprague-Dawley rats. We measured the content and distribution of iron by Perls' staining, and ferritin by immunohistochemical method in the SN. The H & E. cresyl violet, and immunocytochemical stain for glial fibrillary acidic protein, tomato lectin, and cabonic anhydrase-II were done to characterize the exact cell types. Iron content was markedly increased in the hemiparkinsonian model of SNc, not reticulate where normally more iron is distributed. The increased ferritin immunoreactivity was located in the same iron rich area of SNc. The cells with increased iron and ferritin were mainly astrocytes and microglias. 6-OHDA injection into SN resulted in increased free iron and ferritin immunoreactivity, suggesting that iron is important participant in oxidative cell death in PD. We think that increased ferritin in 6 OHDA lesioned SN argues against the hypothesis that decreased ferritin is a prerequisite for the free radical mediated death of nigral neurons in this model.