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    Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys: A possible role for the locus coeruleus in the progression of Parkinson's disease
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    Information on the molecular distribution and ageing trend of brain iron in post‐mortem material from normal subjects is scarce. Because it is known that neuromelanin and ferritin form stable complexes with iron(III), in this study we measured the concentration of iron, ferritin and neuromelanin in substantia nigra from normal subjects, aged between 1 and 90 years, dissected post mortem. Iron levels in substantia nigra were 20 ng/mg in the first year of life, had increased to 200 ng/mg by the fourth decade and remained stable until 90 years of age. The H‐ferritin concentration was also very low (29 ng/mg) during the first year of life but increased rapidly to values of ≈ 200 ng/mg at 20 years of age, which then remained constant until the eighth decade of life. L ‐Ferritin also showed an increasing trend during life although the concentrations were ≈ 50% less than that of H‐ferritin at each age point. Neuromelanin was not detectable during the first year, increased to ≈ 1000 ng/mg in the second decade and then increased continuously to 3500 ng/mg in the 80th year. A Mössbauer study revealed that the high‐spin trivalent iron is probably arranged in a ferritin‐like iron−oxyhydroxide cluster form in the substantia nigra. Based on this data and on the low H‐ and L‐ferritin content in neurones it is concluded that neuromelanin is the major iron storage in substantia nigra neurones in normal individuals.
    Neuromelanin
    We carried out an investigation to identify neuromelanin-containing noradrenergic and dopaminergic neurons in the locus ceruleus and substantia nigra pars compacta of healthy volunteers and patients with Parkinson's disease using a newly developed magnetic resonance imaging technique that can demonstrate neuromelanin-related contrast. The high-resolution neuromelanin images obtained by a 3-T scanner revealed high signal areas in the brain stem and these corresponded well with the location of the locus ceruleus and substantia nigra pars compacta in gross specimens. In Parkinson's disease patients, the signal intensity in the locus ceruleus and substantia nigra pars compacta was greatly reduced, suggesting depletion of neuromelanin-containing neurons. We conclude that neuromelanin magnetic resonance imaging can be used for direct visualization of the locus ceruleus and substantia nigra pars compacta, and may help in detecting pathological changes in Parkinson's disease and related disorders.
    Neuromelanin
    Locus Ceruleus
    Pars compacta
    Locus coeruleus