Ex vivo magnetic resonance imaging in South African manganese mine workers

Criswell, Susan R.; Nelson, Gill; Gonzalez‐Cuyar, Luis F.; Huang, John; Shimony, Joshua S.; Checkoway, Harvey; Simpson, Christopher D.; Dills, Russell L.; Seixas, Noah S.; Racette, Brad A.

doi:10.1016/j.neuro.2015.04.002

Cited by 14 publications

(14 citation statements)

References 39 publications

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“…The authors also noted increased microglial cell density in the basal ganglia. Based on this and their previous study [133] they propose that the pre-clinical stage of Mn-induced neurotoxicity is marked by an initial inflammatory response that may progress to astrocyte isruption and neuronal injury [132]. This would be in agreement with in vitro findings that report a 50 fold higher accumulation of Mn in astrocytes, which may alter their neurotrophic actions and contribute no neuronal injury [134–137].…”

Section: Main Textsupporting

confidence: 82%

“…Even asymptomatic welder apprentices display increased T1 signal in the basal ganglia, but when evaluated in the Grooved Pegboard (for dexterity and fine motor control) or the unified PD rating scale motor subsection 3 (UPDRS3-for parkinsonian signs such as rest and postural tremor, bradykinesia and gait disturbance), the subjects performed within the reference range [131]. Nevertheless important neuropathological alterations have been observed even in the absence of motor symptoms [129, 132, 133]. It is not clear from the clinical studies, however, whether Mn facilitates the development of PD or induces a distinct parkinsonian syndrome.…”

Section: Main Textmentioning

confidence: 99%

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“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Peres

Schettinger

Chen

et al. 2016

BMC Pharmacol Toxicol

280

183

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Manganese (Mn) is an essential heavy metal. However, Mn’s nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication. We report that exposure to Mn may arise from environmental sources, occupational settings, food, total parenteral nutrition (TPN), methcathinone drug abuse or even genetic factors, such as mutation in the transporter SLC30A10. Accumulation of Mn occurs mainly in the basal ganglia and leads to a syndrome called manganism, whose symptoms of cognitive dysfunction and motor impairment resemble Parkinson’s disease (PD). Various neurotransmitter systems may be impaired due to Mn, especially dopaminergic, but also cholinergic and GABAergic. Several proteins have been identified to transport Mn, including divalent metal tranporter-1 (DMT-1), SLC30A10, transferrin and ferroportin and allow its accumulation in the central nervous system. Parallel to identification of Mn neurotoxic properties, neuroprotective strategies have been reported, and these include endogenous antioxidants (for instance, vitamin E), plant extracts (complex mixtures containing polyphenols and non-characterized components), iron chelating agents, precursors of glutathione (GSH), and synthetic compounds that can experimentally afford protection against Mn-induced neurotoxicity.

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Section: Main Textsupporting

confidence: 82%

Section: Main Textmentioning

confidence: 99%

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Peres

Schettinger

Chen

et al. 2016

BMC Pharmacol Toxicol

280

183

View full text Add to dashboard Cite

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“…Long et al (2014) assessed Fe concentration via T2* and, when compared to controls, found full-time welders had lower T2* in the frontal cortex, but no difference in selected subcortical regions of interests (ROIs; e.g., globus pallidus, thalamus, and hippocampus). A recent study in deceased mine workers reported no differences in Fe tissue concentrations in the basal ganglia compared to controls (Criswell et al, 2015), although increased Fe tissue concentration was reported in the basal ganglia of Mn-exposed monkeys (Olanow et al, 1996). …”

Section: Introductionmentioning

confidence: 94%

Association of neurobehavioral performance with R2* in the caudate nucleus of asymptomatic welders

et al. 2017

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Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neuro-toxicity. Although welding-related airborne Fe levels are about ten-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose-response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain MRI were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole blood Fe levels compared to controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole blood Fe concentration. The present study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance.

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“…Welding fumes contain several metals including copper (Cu), Mn, and Fe that may interact to influence welding-related neurotoxicity. Although airborne Fe concentrations are about ten-fold greater than those of Mn (Ellingsen et al, 2006; Flynn and Susi, 2009) and whole blood Fe levels are much higher than those of Mn (Lu et al, 2005), past welding-related studies have focused on Mn accumulation in brain (Choi et al, 2007; Lee et al, 2015), with few studies examining brain deposition of Fe in welders or mine workers (Criswell et al, 2015; Long et al, 2014).…”

Section: Neurotoxic Effects Of Fe At Low-level Mn Exposurementioning

confidence: 99%

Welding-related brain and functional changes in welders with chronic and low-level exposure

et al. 2018

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Although an essential nutrient, manganese (Mn) can be toxic at high doses. There is, however, uncertainty regarding the effects of chronic low-level Mn-exposure. This review provides an overview of Mn-related brain and functional changes based on studies of a cohort of asymptomatic welders who had lower Mn-exposure than in most previous work. In welders with low-level Mn-exposure, we found: 1) Mn may accumulate in the brain in a non-linear fashion: MRI R1 (1/T1) signals significantly increased only after a critical level of exposure was reached (e.g., ≥300 welding hours in the past 90days prior to MRI). Moreover, R1 may be a more sensitive marker to capture short-term dynamic changes in Mn accumulation than the pallidal index [T1-weighted intensity ratio of the globus pallidus vs. frontal white matter], a traditional marker for Mn accumulation; 2) Chronic Mn-exposure may lead to microstructural changes as indicated by lower diffusion tensor fractional anisotropy values in the basal ganglia (BG), especially when welding years exceeded more than 30 years; 3) Mn-related subtle motor dysfunctions can be captured sensitively by synergy metrics (indices for movement stability), whereas traditional fine motor tasks failed to detect any significant differences; and 4) Iron (Fe) also may play a role in welding-related neurotoxicity, especially at low-level Mn-exposure, evidenced by higher R2* values (an estimate for brain Fe accumulation) in the BG. Moreover, higher R2* values were associated with lower phonemic fluency performance. These findings may guide future studies and the development of occupation- and public health-related polices involving Mn-exposure.

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Ex vivo magnetic resonance imaging in South African manganese mine workers

Cited by 14 publications

References 39 publications

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Association of neurobehavioral performance with R2* in the caudate nucleus of asymptomatic welders

Welding-related brain and functional changes in welders with chronic and low-level exposure

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