A nuclear microscopic and histochemical study of iron concentrations and distribution in the midbrain of two age groups of monkeys unilaterally injected with MPTP.

The present study was carried out to elucidate the concentration and distribution of iron in the substantia nigra of two age groups of monkeys after experimental hemi-Parkinsonism induced by unilateral internal carotid injections of MPTP. Iron levels and distribution were detected using the nuclear microscope, which is able to provide structural and quantitative elemental analysis of biological tissue down to the parts per million (ppm) level of analytical sensitivity. Five weeks after unilateral lesioning with MPTP, we observed a 30-65% loss of neurons in the injected substantia nigra of each monkey, compared with the contralateral control 'non-lesioned' side. In monkeys less than 7 years of age, the iron was distributed fairly uniformly and showed little evidence of focal deposits. In monkeys greater than 7 years of age, we observed many dense focal deposits of iron in the substantia nigra. A comparison between iron distributions in nuclear microscopic scans and cell distributions in the same sections stained by the Nissl technique showed that areas containing high iron concentrations were present not where large-diameter neurons with abundant Nissl substance (presumed dopaminergic neurons) were located but in a region ventral to these cell bodies, i.e., in the substantia nigra pars reticulata. These distributions were present on the control side as well as the MPTP-injected side. Since a previous study has shown that unilateral MPTP injection results in lesions of the substantia nigra of the same side but negligible injury to the opposite side, this implies that the iron deposits existed in the older monkeys before MPTP injections (i.e. they occurred normally). The accumulation of iron in the substantia nigra with age suggests the possibility of localised damage to neurons through the catalysis of free radicals.