DEGENERATION OF NIGROSTRIATAL DOPAMINERGIC-NEURONS INCREASES IRON WITHIN THE SUBSTANTIA-NIGRA - A HISTOCHEMICAL AND NEUROCHEMICAL STUDY

Parkinson's-diseased (PD) brains have increased levels of iron in the zona compacta of the substantia nigra (SNc). To determine whether thes e elevated nigral iron levels may be caused secondarily by degeneratio n of nigrostriatal dopaminergic (NS-DA) neurons, the NS-DA pathway was unilaterally lesioned in rats through 6-hydroxydopamine (6-OHDA) infu sion and nigral iron levels evaluated three weeks later. A significant increase was observed in both iron concentration (+35%) and iron cont ent (+33) within the substantia nigra (SN) ipsilateral to comprehensiv e 6-OHDA lesions. Moreover, ferric iron staining was dramatically incr eased within the SNc following 6-OHDA lesions, primarily due to the ap pearance of iron-positive SNc neurons and infiltrating reactive glial cells. Iron staining in the SN zona reticularis was modestly increased after 6-OHDA lesions, but staining in the neostriatum and globus pall idus was unaffected. These results indicate that loss of NS-DA neurons is associated with increased iron levels in the SN. This suggests tha t increased nigral iron levels in PD may be secondary to some neurodeg enerative process. Nonetheless, even a secondary increase in nigral ir on levels may be of pathogenic importance in PD because of iron's abil ity to catalyze neurotoxic free radical formation and perpetuate neuro degeneration.