Manganese: Recent advances in understanding its transport and neurotoxicity

Aschner, Michael; Guilarte, Tomás R.; Schneider, Jay S.; Zheng, Wei

doi:10.1016/j.taap.2007.03.001

Cited by 563 publications

(424 citation statements)

References 152 publications

(191 reference statements)

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“…6h) in agreement with the observation that the uptake, transport, and storage of Mn 2+ ions by nerve cells are associated with those of iron and that both iron and manganese concentrations in the GP are the highest in the brain. 66 The GP is most clearly contrasted from neighboring WM (black arrows in Fig. 6h) where myelin hinders the diffusion of Mn 2+ ions.…”

Section: Nerve Cellsmentioning

confidence: 96%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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This article provides an overview of in vivo magnetic resonance (MR) imaging contrasts obtained for mammalian brain in relation to histological knowledge. Emphasis is paid to the (1) significance of high spatial resolution for the optimization of T 1 , T 2 , and magnetization transfer contrast, (2) use of exogenous extra-and intracellular contrast agents for validating endogenous contrast sources, and (3) histological structures and biochemical compounds underlying these contrasts and (4) their relevance to neuroradiology. Comparisons between MR imaging at subnanoliter resolution and histological data indicate that (a) myelin sheaths, (b) nerve cells, and (c) the neuropil are most responsible for observed MR imaging contrasts, while (a) diamagnetic macromolecules, (b) intracellular paramagnetic ions, and (c) extracellular free water, respectively, emerge as the dominant factors. Enhanced relaxation rates due to paramagnetic ions, such as iron and manganese, have been observed for oligodendrocytes, astrocytes, microglia, and blood cells in the brain as well as for nerve cells. Taken together, a plethora of observations suggests that the delineation of specific structures in high-resolution MR imaging of mammalian brain and the absence of corresponding contrasts in MR imaging of the human brain do not necessarily indicate differences between species but may be explained by partial volume effects. Second, paramagnetic ions are required in active cells in vivo which may reduce the magnetization transfer ratio in the brain through accelerated T 1 recovery. Third, reductions of the magnetization transfer ratio may be more sensitive to a particular pathological condition, such as astrocytosis, microglial activation, inflammation, and demyelination, than changes in relaxation. This is because the simultaneous occurrence of increased paramagnetic ions (i.e., shorter relaxation times) and increased free water (i.e., longer relaxation times) may cancel T 1 or T 2 effects, whereas both processes reduce the magnetization transfer ratio.

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Section: Nerve Cellsmentioning

confidence: 96%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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“…Mercury (Hg) is a chemical contaminant affecting the nervous system when present under the methylated form (Aschner and Syversen, 2005). Its toxicity is of particular concern given its ability to cross the placental barrier and induce damages to the fetus and children at early stages of the development (Folven et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Comparison of a toxicokinetic and a questionnaire-based approach to assess methylmercury intake in exposed individuals

Noisel

Bouchard

Carrier

et al. 2010

J Expo Sci Environ Epidemiol

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Methylmercury (MeHg) is a neurotoxic contaminant and one of the main sources of exposure in humans is seafood consumption. It is thus of interest to assess precisely MeHg exposure. The objective of this study was to estimate MeHg daily intake in exposed individuals using two different approaches, a food questionnaire and toxicokinetic modeling, and compare the complementary and use of each method. For this purpose, a group of 23 fishermen from northern Quebec provided blood and hair samples and answered a standard food questionnaire focusing on seafood consumption. A published and validated toxicokinetic model was then used to reconstruct MeHg daily intakes from mercury (Hg) measurements in biological samples. These intakes were compared to those estimated using a standard food questionnaire on seafood consumption. Daily intakes of MeHg from seafood (mean/median (range)) estimated from hair concentrations with the toxicokinetic-based approach were 6.1/5.2 (0.0-19) mg/day. These intake values were on average six times lower than those estimated using a food questionnaire, that is, 49/32 (7.2-163) mg/day. No correlation was found between the toxicokinetic-based and the questionnaire estimates of MeHg daily intakes. Most of the MeHg intakes estimated with the food questionnaire (21/23) exceeded the US EPA RfD of 0.1 mg/kg bw/day, whereas only a small proportion (6/23) of modeled estimates exceeded the RfD. This study shows that human health risk estimates strongly depend on the chosen approach.

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“…It is critical for antioxidant functions because mitochondrial superoxide dismutase requires Mn as a cofactor (MnSOD) (2). Mn is also a cofactor for a number of enzymes involved in amino acid, lipid, and carbohydrate metabolism, and it plays important roles in immune function, bone, and connective tissue growth (3).…”

mentioning

confidence: 99%

Ferroportin deficiency impairs manganese metabolism in flatiron mice

Seo

Wessling‐Resnick

2015

FASEB j.

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We examined the physiologic role of ferroportin (Fpn) in manganese (Mn) export using flatiron (ffe/+) mice, a genetic model of Fpn deficiency. Blood (0.0123 vs. 0.0107 mg/kg; P = 0.0003), hepatic (1.06 vs. 0.96 mg/kg; P = 0.0125), and bile Mn levels (79 vs. 38 mg/kg; P = 0.0204) were reduced in ffe/+ mice compared to +/+ controls. Erythrocyte Mn-superoxide dismutase was also reduced at 6 (0.154 vs. 0.096, P = 0.0101), 9 (0.131 vs. 0.089, P = 0.0162), and 16 weeks of age (0.170 vs. 0.090 units/mg protein/min; P < 0.0001). 54 Mn uptake after intragastric gavage was markedly reduced in ffe/+ mice (0.0187 vs. 0.0066% dose; P = 0.0243), while clearance of injected isotope was similar in ffe/+ and +/+ mice. These values were compared to intestinal absorption of 59 Fe, which was significantly reduced in ffe/+ mice (8.751 vs. 3.978% dose; P = 0.0458). The influence of the ffe mutation was examined in dopaminergic SH-SY5Y cells and human embryonic HEK293T cells. While expression of wild-type Fpn reversed Mn-induced cytotoxicity, ffe mutant H32R failed to confer protection. These combined results demonstrate that Fpn plays a central role in Mn transport and that flatiron mice provide an excellent genetic model to explore the role of this exporter in Mn homeostasis.-Seo, Y. A., Wessling-Resnick, M. Ferroportin deficiency impairs manganese metabolism in flatiron mice. FASEB J. 29, 2726-2733 (2015). www.fasebj.org

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Manganese: Recent advances in understanding its transport and neurotoxicity

Cited by 563 publications

References 152 publications

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

Comparison of a toxicokinetic and a questionnaire-based approach to assess methylmercury intake in exposed individuals

Ferroportin deficiency impairs manganese metabolism in flatiron mice

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