Iron concentrations and distributions in the parkinsonian substantia nigraof aged and young primate models

Parkinson's disease (PD) is a progressive neuronal degenerative brain disea se of the elderly, and is caused by the selective degeneration of neurons i n the substantia nigra (SN) region of the brain, resulting in a reduced pro duction of the neurotransmitter dopamine. Iron has been linked to dopaminer gic cell death in Parkinson's disease because of its potential to promote f ree radicals, leading to oxidative stress. The present study is aimed at us ing the techniques of nuclear microscopy to elucidate the iron concentratio ns and distributions in the SN of both young and old monkeys following unil ateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioning. A group of three old monkeys (older than 7 years) and a group of three youn g monkeys (younger than 7 years) were unilaterally MPTP-lesioned (right sid e) to induce parkinsonism and sacrificed after 35 days. The left side SN wa s used as a control. This time interval was chosen to correspond to an aver age 50% loss of dopamine producing cells in the lesioned right side SN, We have observed a significant difference in iron concentrations between the S Ns of the young and old monkeys (increasing from an average of 233 to 1092 parts per million dry weight). When comparing the lesioned and non-lesioned SNs of the same animal, we found no significant difference in iron levels for each young monkey. However we have found a slight increase in iron (app roximately 10%) between the lesioned SN and control SN for old monkeys. We have also observed that in the SN of younger primates, there is a weak anti -correlation in the SN iron levels with the neuron distribution. In the old er monkeys, however, we have observed a proliferation of iron-rich granules , which appear to be more strongly anti-correlated with the distribution of neurons. The iron-cell anti-correlation occurs both in the control as well as the lesioned SN. Our results suggest that iron, particularly in the for m of iron-rich deposits, accumulates in specific sites in the SN with age. Since Parkinson's disease mainly occurs in the elderly, this may implicate iron as a factor in dopaminergic cell death through iron-catalysed free rad ical production. (C) 2001 Elsevier Science B.V. All rights reserved.