Iron and Other Metals in Neuromelanin, Substantia Nigra, and Putamen of Human Brain

Abstract

Radiochemical neutron activation analysis has been used to determine the concentration of 36 elements in neuromelanin, 22 elements in substantia nigra, and 32 elements in putamen of healthy subjects without signs of neurological disorders. Substantia nigra and putamen tissues were carefully dissected from the brain using special surgical instruments and tools as well as an adequate sampling procedure to avoid the risk of metal contamination during sampling. Neuromelanin was isolated from putamen by a multiple‐step procedure (extraction with phosphate buffer, lipid and protein elimination by methanol extraction, and sodium dodecyl sulfate‐proteinase). The isolated pigment as well as substantia nigra and putamen underwent neutron activation analysis involving irradiation in a high‐neutron‐flux reactor, radiochemical separations, and counting of the induced radionuclides by computer‐based γ‐ray spectrometry. Iron was the element present in the highest concentration in all analyzed samples. The amount of iron was similar in substantia nigra and putamen (3,000 and 3,830 ng/mg wet weight, respectively) and 10 times higher in neuromelanin (30,800 ng/mg dry weight). Zinc was also present at high levels in three samples, ranging from 16.8 (substantia nigra) to 1,500 ng/mg (neuromelanin). Elements such as Zn, Cr, Se, Sr, Co, Sb, Ni, Hg, Ce, Au, Ag, Ta, and Sc were present in neuromelanin at much higher concentrations than in substantia nigra and putamen. These findings indicate that substantia nigra and putamen contain metals at higher concentrations than observed in blood and that neuromelanin has a particular affinity for metals.

The comparative biology of neuromelanin and lipofuscin in the human brain

“…The insoluble fraction of the pigment can be isolated from the human brain using methods widely used to isolate NM [Dedov et al, unpublished data]. Reports that NM can be isolated from brain regions not known to contain this pigment [83] perhaps result from the isolation of lipofuscin from these areas.…”

Redox Mechanism of Neurotoxicity by a Serotonin–Acrolein Polymeric Melanoid

“…Membrane-enclosed neuromelanin is a well-known feature of pigmented neurons (Sulzer et al 2000). Neuromelanin is thought to provide neuroprotection (Lindquist et al 1988;Zecca et al 1994) with anti-oxidative properties (Wilczok et al 1999). SDM, which results from lipid peroxidation, may counter the protective effects of native neuromelanin.…”

Metal Catalyzed Oxidation of Alpha-Synuclein – A Role for Oligomerization in Pathology?

“…In addition, oxidation, condensation and polymerization of cytosolic DA and its metabolites results in formation of an insoluble pigment called neuromelanin (NM) that accumulates with aging in the SN of humans, and to a lesser extent, in other primates. A normally protective role for NM is likely, given its ability to sequester a variety of potentially toxic substances, such as redox-active DA metabolites and metals, especially iron, and toxins such as *Address correspondence to this author at the Laboratory of Biochemistry, National Heart Lung and Blood Institute, 50 South Drive MSC 8012, Bethesda, Maryland 20892, USA; Tel: (301) 435-8234; Fax: (301) 496-0599; E-mail: ncole@mail.nih.gov MPP+ and pesticides [9][10][11][12]. In addition, approx.…”