From Manganism to Manganese-Induced Parkinsonism: A Conceptual Model Based on the Evolution of Exposure

Department of Experimental and Applied Medicine, Section of Occupational Health and Industrial Hygiene, University of Brescia, Brescia, Italy.
Neuromolecular medicine (Impact Factor: 3.68). 12/2009; 11(4):311-21. DOI: 10.1007/s12017-009-8108-8
Source: PubMed


Manganism is a distinct medical condition from Parkinson's disease. Manganese exposure scenarios in the last century generally have changed from the acute, high-level exposure conditions responsible for the occurrence of manganism to chronic exposure to much lower levels. Such chronic exposures may progressively extend the site of manganese deposition and toxicity from the globus pallidus to the entire area of the basal ganglia, including the substantia nigra pars compacta involved in Parkinson's disease. The mechanisms of manganese neurotoxicity from chronic exposure to very low levels are not well understood, but promising information is based on the concept of susceptibility that may place individuals exposed to manganese at a higher risk for developing Parkinsonian disturbances. These conditions include mutations of genes which play important pathogenetic roles in both Parkinsonism and in the regulation of manganese transport and metabolism. Liver function is also important in manganese-related neurotoxicity and sub-clinical impairment may increase the risk of Parkinsonism. The purpose and scope of this report are to explore the literature concerning manganese exposure and potential subclinical effects and biological pathways, impairment, and development of diseases such as Parkinsonism and manganism. Inhalation and ingestion of manganese will be the focus of this report.

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Available from: Roberto Lucchini
    • "There has also been increasing concern regarding the role of environmental manganese exposure and children's health (Zoni and Lucchini, 2013). For example, several community studies have suggested a link between manganese content in drinking water and a decrease in the IQ of children (Bouchard et al., 2011;Khan et al., 2012;Wasserman et al., 2006), although the toxicological significance of these studies remains to be established (Lucchini et al., 2009). Many questions remain as to the conditions under which ingestion of manganese can result in an increased incidence of human neurological disease (Boyes, 2010). "
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    ABSTRACT: Concerns exist as to whether individuals may be at greater risk for neurotoxicity following increased manganese (Mn) oral intake. The goals of this study were to determine the equivalence of three methods of oral exposure and the rate (mg Mn/kg/day) of exposure. Adult male rats were allocated to control diet (10 ppm), high manganese diet (200 ppm), manganese-supplemented drinking water, and manganese gavage treatment groups. Animals in the drinking water and gavage groups were given the 10 ppm manganese diet and supplemented with manganese chloride (MnCl2) in drinking water or once-daily gavage to provide a daily manganese intake equivalent to that seen in the high-manganese diet group. No statistically significant difference in body weight gain or terminal body weights was seen. Rats were anesthetized following 7 and 61 exposure days, and samples of bile and blood were collected. Rats were then euthanized and striatum, olfactory bulb, frontal cortex, cerebellum, liver, spleen, and femur samples were collected for chemical analysis. Hematocrit was unaffected by manganese exposure. Liver and bile manganese concentrations were elevated in all treatment groups on day 61 (relative to controls). Increased cerebellum manganese concentrations were seen in animals from the high manganese diet group (day 61, relative to controls). Increased (relative to all treatment groups) femur, striatum, cerebellum, frontal cortex, and olfactory bulb manganese concentrations were also seen following gavage suggesting that dose rate is an important factor in the pharmacokinetics of oral manganese. These data will be used to refine physiologically-based pharmacokinetic models, extending their utility for manganese risk assessment by including multiple dietary exposures. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email:
    No preview · Article · Feb 2015 · Toxicological Sciences
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    • "Among others, manganese mining, welding and manufacturing workers, welders in stainless steel facilities exposed to fumes and dusts are considered professional groups at risk of occupational exposure to metal NPs. In these cases it has been found that manganese NPs were transported through the axons of olfactory neurons from the nasal epithelium to the olfactory bulb of the brain and a progressive damage of functioning in the central nervous system has been evidenced [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [109] [110] [111] [112] [113] [114] [115] [116] [117]. "
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    • "Manganism is characterized by variety of psychiatric, cognitive and motor disturbances that resemble those inherent to Parkinson’s disease (PD) [4]. However, the primary brain regions targeted by Mn are the globus pallidus and striatum of the basal ganglia, whereas neurodegeneration in PD is predominantly confined to the substantia nigra [5]. "
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    ABSTRACT: Astrocytes are responsible for numerous aspects of metabolic support, nutrition, control of the ion and neurotransmitter environment in central nervous system (CNS). Failure by astrocytes to support essential neuronal metabolic requirements plays a fundamental role in the pathogenesis of brain injury and the ensuing neuronal death. Astrocyte-neuron interactions play a central role in brain homeostasis, in particular via neurotransmitter recycling functions. Disruption of the glutamine (Gln)/glutamate (Glu) -gamma-aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons contributes to changes in Glu-ergic and/or GABA-ergic transmission, and is associated with several neuropathological conditions, including manganese (Mn) toxicity. In this review, we discuss recent advances in support of the important roles for astrocytes in normal as well as neuropathological conditions primarily those caused by exposure to Mn.
    Full-text · Article · Apr 2013 · BMC pharmacology & toxicology
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