Manganese action in brain function

Takeda, Atsüshi

doi:10.1016/s0165-0173(02)00234-5

Cited by 503 publications

(366 citation statements)

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“…Moreover, Mn plays a role in the modulation of the immune system, and in protein, lipid and carbohydrate metabolism (Addess et al, 1997;Aschner et al, 1992;Fitsanakis et al, 2005;Malecki et al, 1999). Evidence also corroborates the involvement of Mn in the stellate process production in astrocytes (Liao et al, 2001), as well as in the metabolism of brain glutamate to glutamine, a step carried out by the astrocyte-specific enzyme, glutamine synthetase (Wedler et al, 1982;Wedler et al, 1984;Takeda, 2003).Despite its essentiality in multiple metabolic functions, Mn can be toxic at high concentrations. The brain, in particular, is highly susceptible to Mn toxicity.…”

supporting

confidence: 54%

“…Mn toxicity from dietary intake is rare; its uptake is tightly regulated, and any excess of ingested Mn is readily excreted via the bile. In contrast, both pulmonary uptake and particulate transport via the olfactory bulb (Saric, 1986;Aschner et al, 1991;Thompson et al, 2007) can lead to deposition of Mn within the striatum and cerebellum and inflammation of the nasal epithelium .Mn plays an important role in the development and functioning of the brain (Prohaska, 1987;Takeda, 2003). Mn deficiency may result in birth defects, poor bone formation and an increased susceptibility to seizures (Aschner, 2000;Aschner et al, 2002).…”

mentioning

confidence: 99%

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Manganese transport in eukaryotes: The role of DMT1

2008

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Manganese (Mn) is a transition metal that is essential for normal cell growth and development, but is toxic at high concentrations. While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson's disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia (Calne et al., 1994;Dobson et al., 2004).Mn-induced motor neuron diseases have been the subjects of numerous studies; however, this review is not intended to discuss its neurotoxic potential or its role in the etiology of motor neuron disorders. Rather, it will focus on Mn uptake and transport via the orthologues of the divalent metal transporter (DMT1) and its possible implications to Mn toxicity in various categories of eukaryotic systems, such as in vitro cell lines, in vivo rodents, the fruitfly, Drosophila melanogaster, the honeybee, Apis mellifera L., the nematode, Caenorhabditis elegans, and the baker's yeast, Saccharomyces cerevisiae. Keywords DMT1; Manganese; NRAMP-2; Transport ManganeseMn is one of the most abundant naturally occurring elements in the earth's crust; it does not occur naturally in a pure state. Oxides, carbonates and silicates are the most important Mncontaining minerals (Post, 1999). Depending on its oxidation state, Mn is utilized in countless industrial processes, such as the production of dry cell batteries, steel (Post, 1999; Saric, 1986), fuel oil additives and antiknock agents (Pfeifer et al., 2004;Ressler et al., 1999;Rollin et al., 2005). *Corresponding Author: Michael Aschner, PhD, 2215-B Garland Avenue, 11425 MRB IV, Vanderbilt University Medical Center, Nashville, michael.aschner@vanderbilt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurotoxicology. Author manuscript; available in PMC 2009 July 1. Published in final edited form as:Neurotoxicology. 2008 July ; 29(4): 569-576. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe major source of Mn in humans is through dietary ingestion. Approximately 3-5% of ingested Mn is absorbed across the intestinal wall, and the remainder is excreted in feces, representing tight homeostatic control over Mn absorption. Mn toxicity from dietary intake is rare; its uptake is tightly regulated, and any excess of ingested Mn is readily excreted via the bile. In contrast, both pulmonary uptake and particulate transport via the olfactory bulb (Saric, 1986;Aschner et al., 1991...

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confidence: 54%

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confidence: 99%

Manganese transport in eukaryotes: The role of DMT1

2008

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“…The latter provides further evidence that the reported differential manganese accumulation in the runners and sedentary rats is caused by difference in the functional load in a specific subset of brain structures. On the other hand, we cannot exclude the possibility that the increased accumulation of manganese in the functionally activated brain regions -at least to some extent -results from an accelerated direct transport of manganese from the blood stream across BBB of the cerebral capillaries via a non-specific metal transporters (Takeda, 2003). It has been shown that at high plasma concentrations transport across the choroid plexus is more prevalent, while at normal plasma concentrations the transport across cerebral capillaries dominates (Murphy et al, 1991;Rabin et al, 1993); the latter could be true in case of low doses of manganese.…”

Section: Discussionmentioning

confidence: 98%

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

et al. 2010

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Magnetic resonance imaging (MRI) is widely used in basic and clinical research to map the structural and functional organization of the brain. An important need of MR research is for contrast agents that improve soft-tissue contrast, enable visualization of neuronal tracks, and enhance the capacity of MRI to provide functional information at different temporal scales. Unchelated manganese can be such an agent, and manganese-enhanced MRI (MEMRI) can potentially be an excellent technique for localization of brain activity (for review see Silva et al., 2004). Yet, the toxicity of manganese presents a major limitation for employing MEMRI in behavioral paradigms. We have tested systematically the voluntary wheel running behavior of rats after systemic application of MnCl 2 in a dose range of 16-80 mg/kg, which is commonly used in MEMRI studies. The results show a robust dose-dependent decrease in motor performance, which was accompanied by weight loss and decrease in food intake. The adverse effects lasted for up to 7 postinjection days. The lowest dose of MnCl 2 (16 mg/kg) produced minimal adverse effects, but was not sufficient for functional mapping. We have therefore evaluated an alternative method of manganese delivery via osmotic pumps, which provide a continuous and slow release of manganese. In contrast to a single systemic injection, the pump method did not produce any adverse locomotor effects, while achieving a cumulative concentration of manganese (80 mg/kg) sufficient for functional mapping. Thus, MEMRI with such an optimized manganese delivery that avoids toxic effects can be safely applied for longitudinal studies in behaving animals.

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“…Its properties have led to its extensive use in studies assessing the negative effects of Mn on the basal ganglia (Bird et al, 1984;Sloot et al, 1994;Cano et al, 1997;Takeda, 2003). However, the basis for the use of MnSO 4 and MnPO 4 in this study lies in the fact that they are the two major combustion products of MMT, a gasoline additive used in certain countries and approved for use in the U.S. (Lynam et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

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Following combustion of fuel containing the additive methylcyclopentadienyl-manganesetricarbonyl (MMT), manganese phosphate (MnPO 4 ) and manganese sulfate (MnSO 4 ) are emitted in the atmosphere. Manganese chloride (MnCl 2 ), another Mn 2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO 4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl 2 or MnSO 4 ; antioxidants were partially protective. Also, both MnCl 2 and MnPO 4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO 4 will be more potent in forming aminochrome than MnCl 2 or MnSO 4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO 4 in particular, is the generation of reactive DA intermediates.

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Manganese action in brain function

Cited by 503 publications

References 100 publications

Manganese transport in eukaryotes: The role of DMT1

Manganese transport in eukaryotes: The role of DMT1

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

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