MANGANESE - A TRANSITION-METAL PROTECTS NIGROSTRIATAL NEURONS FROM OXIDATIVE STRESS IN THE IRON-INDUCED ANIMAL-MODEL OF PARKINSONISM

It has been suggested that transition metals such as iron and manganes e produce oxidative injury to the dopaminergic nigrostriatal system, w hich may play a critical role in the pathogenesis of Parkinson's disea se. Intranigral infusion of ferrous citrate (0 to 5.4 nmol. i.n.) acut ely increased lipid peroxidation in the substantia nigra and dopamine turnover in the caudate nucleus. Subsequently, it caused a severe depl etion of dopamine levels in the rat caudate nucleus. In contrast to ir on's pro-oxidant effect, manganese (up to 30 nmol, i.n.) causes neithe r lipid peroxidation nor nigral injury/dopamine depletion. Manganese ( 1.05 to 4.2 nmol, i.n.) dose-dependently protected nigral neurons from iron-induced oxidative injury and dopamine depletion. Manganese also suppressed acute increase in dopamine turnover and contralateral turni ng behaviour induced by iron. In brain homogenates manganese (0 to 10 mu M) concentration-dependently inhibited propagation of lipid peroxid ation caused by iron (0 to 5 mu M). Without the contribution of mangan ese-superoxide dismutase manganese was still effective in sodium azide and/or heat-pretreated brain homogenates. Surprisingly, iron but not manganese, catalysed the Fenton reaction or the conversion of hydrogen peroxide to hydroxyl radicals. The results indicate that iron and man ganese are two transition metals mediating opposite effects in the nig rostriatal system, as pro-oxidant and antioxidant, respectively. In co nclusion, intranigral infusion of iron, but not manganese, provides an animal model for studying the pathophysiological role of oxidant and oxidative stress in nigrostriatal degeneration and Parkinsonism. The p resent results further suggest that the atypical antioxidative propert ies of manganese may protect substantia nigra compacta neurons from ir on-induced oxidative stress. (C) 1998 IBRO. Published by Elsevier Scie nce Ltd.