Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet, a low-Fe diet (ID), or a low-Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (postnatal days [PN] 4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe, increased plasma transferrin (Tf), and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased Tf and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including Mn, chromium, zinc, cobalt, aluminum, molybdenum, and vanadium. Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter-1 and transferrin receptor were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn.

In studies of trace elements in biological tissue, it is imperative that sample handling does not substantially change element concentrations. In many cases, fresh tissue is not available for study, but formalin-fixed tissue is. Formalin fixation has the potential to leach elements from the tissue, but few studies have been published in this area. The concentrations of 19 elements were determined by high-resolution inductively coupled plasma mass spectrometry in formalin in which human and rat brain samples had been stored for different time durations ranging from weeks up to several years. Additional analysis was carried out in fixed brain samples. There was substantial leaching of elements from the tissue into the formalin, and the leaching varied considerably between different elements. For example, formalin concentrations of As, Cd, Mg, Rb, and Sb increased more than 100-fold upon long-term (years) storage, while for Ni and Cr, the leaching was negligible. The degree of leaching was strongly time-dependent. In conclusion, formalin fixation and storage of biological tissue has the potential to leach substantial fractions of several trace elements from the tissue. The potential of leaching must be critically considered when using formalin-fixed biological tissue in trace metal analysis.

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. However, virtually nothing is known regarding excess Mn accumulation during central nervous system development. Developing rats were exposed to a diet high in Mn via maternal milk during lactation (PN4-21). The high Mn diet resulted in changes in hematological parameters similar to those seen with iron (Fe) deficiency in dams (decreased plasma Fe; increased plasma transferrin [Tf]) and pups (decreased hemoglobin [Hb] and plasma Fe; increased plasma Tf and total iron binding capacity). Mn-exposed pups showed an increase in brain Mn, chromium, and zinc concurrent with a decrease in brain Fe. In conjunction with the altered transport and distribution of essential metals within the brain, there was enhanced protein expression of the divalent metal transporter-1 (DMT-1) and transferrin receptor (TfR) overall in the brain; there was a general increase in each region analyzed (cerebellum, cortex, hippocampus, midbrain, and striatum). Neurochemical changes were observed as an increase in gamma-aminobutyric acid (GABA) and the ratio of GABA to glutamate, indicating enhanced inhibitory transmission in the brain. The results of this study demonstrate that developing rats undergo alterations in the transport and distribution of essential metals translating to neurochemical perturbations after maternal exposure to a diet supplemented with excess levels of Mn.

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Trace element analysis of human hair has the potential to reveal retrospective information about an individual's nutritional status and exposure. As trace elements are incorporated into the hair during the growth process, longitudinal segments of the hair may reflect the body burden during the growth period. We have evaluated the potential of human hair to indicate exposure or nutritional status over time by analysing trace element profiles in single strands of human hair. The hair strands from five healthy and occupationally unexposed subjects were cut into 1-cm long segments starting from the scalp. By using high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), we achieved profiles of 12 elements in single strands of human hair, namely, Ag, As, Au, Cd, Cu, Hg, Fe, Pb, Se, Sr, U and Zn. We have shown that trace element analysis along single strands of human hair can yield information about essential and toxic elements, and for some elements, can be correlated with seasonal changes in diet and exposure. The information obtained from the trace element profiles of human hair in this study substantiates the potential of hair as a biomarker.