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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    • "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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    Current Medicinal Chemistry 06/2014; 21(33). DOI:10.2174/0929867321666140601162314 · 3.85 Impact Factor
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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.
    BMC pharmacology & toxicology 04/2013; 14(1):23. DOI:10.1186/2050-6511-14-23
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    • "Chronic low-level exposure to Mn is currently hypothesized as a possible risk factor for the onset of Parkinson's disease [12]. Occupational manganism was closely related to the air Mn concentration in working environment, genetic factors and lifestyles. "
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    ABSTRACT: Background Over exposure to manganese (Mn) can damage the human central nervous system and potentially cause liver toxicity. Alcohol drinking is also one of the well-known harmful factors to hepatic organism. The interaction between Mn exposure and alcohol consumption to liver function was investigated in this study. Methods A total of 1112 on-the-spot workers were included in the cross-sectional survey from a large scale of manganese exposed workers healthy cohort (MEWHC) in a ferro-manganese refinery company. A questionnaire was used to collect the demographic information, occupational history, and alcohol drinking habits. Occupational health examination was carried out for each worker. The five key serum indices, including total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT), and aspartate transaminase (AST), were determined to evaluate the liver function of each subject. Results Workers exposed to high levels of Mn had significantly elevated serum concentrations of liver enzymes (DBILI: 3.84±1.20 μmol/L, ALT: 27.04±19.12 IU/L, and AST: 29.96±16.68 IU/L), when compared to those in the low-exposure group (DBIL: 3.54±0.85 μmol/L, ALT: 20.38±10.97 IU/L, and AST: 26.39±8.07 IU/L), all P<0.01. These serum indices had a significantly increasing trend with the elevation of Mn exposure level (Ptrend <0.01). In addition, the workers with alcohol drinking also showed higher concentrations of liver enzymes than those non-drinkers, especially, and there was significant interaction between Mn exposure and alcohol consumption in terms of these three indices (P<0.001). Conclusions Occupational exposure to Mn can lead to a dose-dependent increase of liver enzyme concentrations, and interact with alcohol drinking to potentially aggravate the liver damage. It will be important for Mn exposed workers to control drinking and also assess liver function in the occupational health examination.
    Environmental Health 04/2013; 12(1):30. DOI:10.1186/1476-069X-12-30 · 3.37 Impact Factor
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