Nervous System Dysfunction among Workers with Long-Term Exposure to Manganese

Mergler, Donna; Huel, Guy; Bowler, Rosemarie M.; Iregren, Anders; Bélanger, Samuel; Baldwin, Mary; Tardif, Robert; Smargiassi, Audrey; Martin, Lauren Drew

doi:10.1006/enrs.1994.1013

Cited by 314 publications

(217 citation statements)

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“…The brain is a critical target organ for Mn deposition as Mn crosses the blood-brain barrier (BBB), and this is the first step in the pathogenesis of the neurotoxicity of Mn. In occupational settings, excessive exposure to Mn via inhalation has been shown to have detrimental effects on the lungs and to accumulate in the brain, causing irreversible brain disease, to some extent similar to Parkinson's disease (PD) [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to manganese in South African coastal communities

Röllin

Kootbodien

Theodorou

et al. 2014

Environ. Sci.: Processes Impacts

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Exposure to environmental sources and altered physiological processes of manganese uptake during pregnancy and its possible effect on prenatal and postnatal development are of concern. This study investigates manganese blood levels at the time of delivery across four cohorts of pregnant women residing in coastal communities of South Africa and examines birth outcomes and environmental factors that could influence manganese levels in the study population. The geometric mean (GM) manganese blood levels (MnB) for all women at delivery was 15.2 µg/L. Collectively, rural women reported higher MnB concentrations (GM, 16.1 µg/L) than urban women (GM, 13.5 µg/L, p<0.001). Of the 302 cord blood samples drawn from the study participants (rural women only), GM MnB levels reported for three rural sites were 25.8 µg/L (Rural 1), 33.4 µg/L (Rural 2) and 43.0 µg/L (Rural 3) and were twice as high as their respective maternal levels. However, no significant correlations were found between maternal and cord MnB levels across the 3 study areas. Factors associated 2 with elevated maternal MnB levels, after adjusting for gestational age were: women living in a rural area (Rural 2) (p = 0.021); women drinking potable water from an outdoor/communal tap sourced from municipality (p = 0.021); drinking water from river/stream (p = 0.036); younger maternal age (p = 0.026); consuming leafy vegetables once a week (p = 0.034); and elevated maternal blood lead concentrations (PbB) (p = 0.002). The results indicate that a MnB concentration in rural women during pregnancy is higher compared to urban women and increases with manganese intake from food and water.

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Section: Introductionmentioning

confidence: 99%

Prenatal exposure to manganese in South African coastal communities

Röllin

Kootbodien

Theodorou

et al. 2014

Environ. Sci.: Processes Impacts

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“…Humans exposed to excess Mn for prolonged periods often exhibit extrapyramidal motor impairments similar to Parkinson's Disease (Calne et al, 1994;Mergler, 1999;Aschner, 2000), as well as cognitive deficits and psychiatric disturbances (Mergler et al, 1994;Aschner, 2000). Although Mn impacts multiple neurotransmitter systems (Fitsanakis et al, 2006b), the complex symptomology characteristic of Mn toxicity suggests that both the mesocorticolimbic and nigrostriatal dopamine systems might be affected.…”

Section: Introductionmentioning

confidence: 99%

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

McDougall¹,

Reichel²,

Farley³

et al. 2008

Neuroscience

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In the present study, we examined whether exposing rats to a high-dose regimen of manganese chloride (Mn) during the postnatal period would depress presynaptic dopamine functioning and alter nonassociative and associative behaviors. To this end, rats were given oral supplements of Mn (750 μg/day) on postnatal days (PD) 1-21. On PD 90, dopamine transporter (DAT) immunoreactivity and [ 3 H]dopamine uptake were assayed in the striatum and nucleus accumbens, while in vivo microdialysis was used to measure dopamine efflux in the same brain regions. The effects of postnatal Mn exposure on nigrostriatal functioning were evaluated by assessing rotorod performance and amphetamine-induced stereotypy in adulthood. In terms of associative processes, both cocaineinduced conditioned place preference (CPP) and sucrose-reinforced operant responding were examined. Results showed that postnatal Mn exposure caused persistent declines in DAT protein expression and [ 3 H]dopamine uptake in the striatum and nucleus accumbens, as well as long-term reductions in striatal dopamine efflux. Rotorod performance did not differ according to exposure condition, however Mn-exposed rats did exhibit substantially more amphetamine-induced stereotypy than vehicle controls. Mn exposure did not alter performance on any aspect of the CPP task (preference, extinction, or reinstatement testing), nor did Mn affect progressive ratio responding (a measure of motivation). Interestingly, acquisition of a fixed ratio task was impaired in Mn-exposed rats, suggesting a deficit in procedural learning. In sum, these results indicate that postnatal Mn exposure causes persistent declines in various indices of presynaptic dopaminergic functioning. Mninduced alterations in striatal functioning may have long-term impact on associative and nonassociative behavior.

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“…This continuum ranges from severe motor dysfunction leading to overt signs of manganism in specific work environments Tanaka and Lieben 1969), and early non-clinical neurofunctional deficits in visual reaction time, eye-hand coordination, and hand steadiness and memory, as well as behavioral effects (lower activity levels, sexual drive, and olfactory perception; fatigue and irritability) (Roels et al 1987(Roels et al , 1992Iregren 1990;Kim et al 2005;Lucchini et al 1995Lucchini et al , 1999Mergler et al 1994). High prevalence of Parkinsonian disturbances was also observed among residents in the vicinities of ferromanganese plants (Lucchini et al 2003).…”

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confidence: 99%

Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

Gwiazda

Lucchini

Smith

2007

Journal of Toxicology and Environmental Health, Part A

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The adequacy of existing animal studies to understand the effects of chronic low-level manganese exposures in humans is unclear. Here, a collection of subchronic to chronic rodent and non-human primate studies was evaluated to determine whether there is a consistent dose -response relationship among studies, whether there is a progression of effects with increasing dose, and whether these studies are adequate for evaluating the neurotoxicity of chronic low-level manganese exposures in humans. Neurochemical and behavioral effects were compared along the axis of estimated internal cumulative manganese dose, independent of the route of exposure. In rodents, motor effects emerged at cumulative doses below those where occupationally exposed humans start to show motor deficits. The main neurochemical effects in rodents were an increase in striatal GABA concentration throughout the internal cumulative dose range of 18 to 5300 mg Mn/Kg but a variable effect on striatal dopamine concentration emerging at internal cumulative doses above ~200 mg Mn/Kg. Monkey studies showed motor deficits and effects on the globus pallidus at relatively low doses and consistent harmful effects on both the globus pallidus and the caudate and putamen at higher doses (> 260 mg Mn/Kg). Internal cumulative manganese doses of animal studies extend more than two orders of magnitude (<1 to 5300 mg Mn/Kg) above the doses at which occupationally exposed humans show neurological dysfunction (10-15 mg Mn/Kg). Since the animal data indicate that manganese neurotoxicity may be different at low compared to elevated exposures, most existing animal model studies might be of 3 limited relevance for the risk assessment of chronic low-level manganese exposure to humans. 4

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Nervous System Dysfunction among Workers with Long-Term Exposure to Manganese

Cited by 314 publications

References 0 publications

Prenatal exposure to manganese in South African coastal communities

Prenatal exposure to manganese in South African coastal communities

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

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