INCREASED IRON IN THE SUBSTANTIA-NIGRA COMPACTA OF THE MPTP-LESIONED HEMIPARKINSONIAN AFRICAN-GREEN MONKEY - EVIDENCE FROM PROTON MICROPROBE ELEMENTAL MICROANALYSIS

The association of free radicals and particularly free iron in the pat hogenesis of idiopathic Parkinson's disease and MPTP-induced parkinson ism remains controversial. Whereas the actual cause of dopamine cell d eath in the substantia nigra compacta (SNc) remains unknown, disturban ces in lipid peroxidation and subsequent mitochondrial and cell membra ne disruption has been demonstrated. In a genetically susceptible host , abnormal elimination of oxygen and trace metal free radicals may fur ther damage dopamine cells. Using a unilaterally MPTP-treated African Green monkey, which showed obvious contralateral hemiparkinsonism, the total free iron concentration was measured. Iron, Fe2+ and Fe3+, but not other trace elements, was significantly elevated in the SNc compar ed with the opposite unlesioned side, which was similar to separate co ntrol animals. Iron content in the SNc, periaqueductal gray area, and crus cerebri was 228-270 ppm. Normal control SNc was 285 (+/-59) ppm, whereas iron levels of 532 (+/-151) ppm were found in the MPTP-lesione d SNc. These animals were drug naive and not on long-term levodopa mai ntenance. Proton microprobe elemental analysis was matched against adj acent immunocytochemically stained tissue slices to ensure the cells s tudied were in the SNc. Iron was found not only in the degenerating do pamine cells themselves but also in the surrounding matrix and glial c ells. Whether free iron that is not bound to neuromelanin is responsib le for dopamine cell death as suggested by these experiments remains t o be proved.