Reversibility of Neuroimaging Markers Influenced by Lifetime Occupational Manganese Exposure

Edmondson, David; Ruoyun, E.; Yeh, Chien Lin; Ward, Eric J.; Snyder, Sandy; Azizi, Elham; Zauber, S. Elizabeth; Wells, Ellen M.; Dydak, Ulrike

doi:10.1093/toxsci/kfz174

Cited by 12 publications

(11 citation statements)

References 46 publications

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“…In welders, thalamic GABA levels were found to be associated with Mn deposition and the rate of Mn exposure, being the highest values observed at high exposure with air Mn levels of 0.23 ± 0.18 mg/m 3 [ 184 ]. Specifically, thalamic GABA levels in welders significantly correlated with air Mn concentrations and cumulative exposure for the last three and 12 months [ 185 ]. However, another study did not observe any association between thalamic and striatal GABA levels and blood Mn or airborne metal exposure levels in welders [ 186 ].…”

Section: Neurotransmissionmentioning

confidence: 99%

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Tinkov

Paoliello

Mazilina

et al. 2021

IJMS

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Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

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Section: Neurotransmissionmentioning

confidence: 99%

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Tinkov

Paoliello

Mazilina

et al. 2021

IJMS

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“…We have shown that neurotransmitter concentration, specifically γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system, is altered with Mn exposure. Specifically, GABA is higher in the thalamus in groups exposed to higher levels of Mn (Ma et al, 2018) and changes proportionately with levels of Mn exposure (Edmondson et al, 2019).…”

Section: Introductionmentioning

confidence: 93%

“…Thalamic GABA-Prior studies (Edmondson et al, 2019;Long et al, 2014;Ma et al, 2018) have shown that thalamic GABA (GABA Thal ) concentrations are correlated with Mn exposure. Therefore, we included GABA Thal as a target variable.…”

Section: 33mentioning

confidence: 99%

“…Similarly, we can use the MRI relaxation rate R1, which is proportional to Mn in the region, to measure Mn uptake, accumulation, and dispersion in the brain (Yeh et al, 2016). This has been done in studies involving rats (Lehallier et al, 2012), monkeys (Dorman, 2006;Park et al, 2007;Shinotoh et al, 1995), and humans (Edmondson et al, 2019;Lee et al, 2018Lee et al, , 2015Lewis et al, 2016;Long et al, 2015;Ma et al, 2018), but understanding the relationship between exposure and uptake is still ongoing. For instance, in monkeys, there was a strong correlation and linear relationship between R1 and Mn accumulation in the various regions of the brain (Dorman, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Whole-brain R1 predicts manganese exposure and biological effects in welders

et al. 2020

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Manganese (Mn) is a neurotoxicant that, due to its paramagnetic property, also functions as a magnetic resonance imaging (MRI) T1 contrast agent. Previous studies in Mn toxicity have shown that Mn accumulates in the brain, which may lead to parkinsonian symptoms. In this article, we trained support vector machines (SVM) using whole-brain R1 (R1 = 1/T1) maps from 57 welders and 32 controls to classify subjects based on their air Mn concentration ([Mn] Air ), Mn brain accumulation (ExMn Brain ), gross motor dysfunction (UPDRS), thalamic GABA concentration (GABA Thal ), and total years welding. R1 was highly predictive of [Mn] Air above a threshold of 0.20 mg/m 3 with an accuracy of 88.8% and recall of 88.9%. R1 was also predictive of subjects with GABA Thal having less than or equal to 2.6 mM with an accuracy of 82% and recall of 78.9%. Finally, we used an SVM to predict age as a method of verifying that the results could be attributed to Mn exposure. We found that R1 was predictive of age below 48 years of age with accuracies ranging between 75% and 82% with recall between 94.7% and 76.9% but was not predictive above 48 years of age. Together, this suggests that lower levels of exposure (< 0.20 mg/m 3 and < 18 years of welding on the job) do not produce discernable signatures whereas higher air exposures and subjects with more total years welding produce signatures in the brain that are readily identifiable using SVM.

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“…На нашу думку, причина розбіжностей пов'язана з особливостями експонування. [11,[20][21][22]. Саме з функціональним дисбалансом медіаторних систем мозку пов'язують порушення секреції гормонів гіпофіза [23].…”

Section: аналіз літературних данихunclassified

Impact of an increased exposure with manganese and nickel on pituitary hormones in women with ovarian polycystosis

Prodanchuk

Татарчук

Gunkov

et al. 2020

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Objective of the study: to evaluate the possible impact of manganese and nickel on the state of gonadotropic pituitary function and prolactin secretion.Materials and methods. For the study 2 groups of women were selected. The control group consisted of 38 women of reproductive age without reproductive system pathology. The main group consisted of 52 women who were diagnosed with polycystic ovarian syndrome (PCOS) in accordance with the Rotterdam Consensus criteria. Mass spectrometry was used in both groups to determine the indicators of manganese and nickel in serum. Evaluation of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin in serum was performed by the enzyme immunoassay. To assess the statistical significance of data (p) we used the Mann-Whitney U-test and Student's t-test. Spearman's coefficient was used for correlation analysis.Results. Studies have shown that women with PCOS compared with the control group showed increased manganese levels (p = 0.0093) and nickel levels (p = 0.00019) in serum. Prolactin (p = 0.0024) and LH levels (p = 0.0001) were increased in the group of women with PCOS too. FSH in both groups practically did not differ (p = 0.074). Significant individual fluctuations in the secretion of gonadotropins and prolactin were observed in the main group. In authors’ opinion, this may be a sign of pituitary dysfunction. Only correlation between manganese-prolactin and manganese-LH levels was found in the group of women with PCOS. There was no relationship between level of trace elements and hormones in all other cases.Conclusion. Increased levels of manganese and nickel in serum were found in women with PCOS. Elevated prolactin and LH levels in women with PCOS may be associated with increased manganese exposure. Nickel exposure does not affect gonadotropin and prolactin levels in women with PCOS.

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Reversibility of Neuroimaging Markers Influenced by Lifetime Occupational Manganese Exposure

Cited by 12 publications

References 46 publications

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Whole-brain R1 predicts manganese exposure and biological effects in welders

Impact of an increased exposure with manganese and nickel on pituitary hormones in women with ovarian polycystosis

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