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Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes

  • Inorganic Compounds
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Abstract

The potential for development of Parkinson’s disease (PD)-like neurological dysfunction following occupational exposure to aerosolized welding fumes (WF) is an area of emerging concern. Welding consumables contain a complex mixture of metals, including iron (Fe) and manganese (Mn), which are known to be neurotoxic. To determine whether WF exposure poses a neurological risk particularly to the dopaminergic system, we treated Sprague–Dawley rats with WF particulates generated from two different welding processes, gas metal arc-mild steel (GMA-MS; low Mn, less water-soluble) and manual metal arc-hard surfacing (MMA-HS; high Mn, more water-soluble) welding. Following repeated intratracheal instillations (0.5 mg/rat, 1/week × 7 weeks) of GMA-MS or MMA-HS, elemental analysis and various molecular indices of neurotoxicity were measured at 1, 4, 35 or 105 days after last exposure. MMA-HS exposure, in particular, led to increased deposition of Mn in striatum and midbrain. Both fumes also caused loss of tyrosine hydroxylase (TH) protein in the striatum (~20%) and midbrain (~30%) by 1 day post-exposure. While the loss of TH following GMA-MS was transient, a sustained loss (34%) was observed in the midbrain 105 days after cessation of MMA-HS exposure. In addition, both fumes caused persistent down-regulation of dopamine D2 receptor (Drd2; 30–40%) and vesicular monoamine transporter 2 (Vmat2; 30–55%) mRNAs in the midbrain. WF exposure also modulated factors associated with synaptic transmission, oxidative stress, neuroinflammation and gliosis. Collectively, our findings demonstrate that repeated exposure to Mn-containing WF can cause persistent molecular alterations in dopaminergic targets. Whether such perturbations will lead to PD-like neuropathological manifestations remains to be elucidated.

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Abbreviations

BALF:

Bronchoalveolar lavage fluid

CCL2:

Chemokine–chemokine ligand 2

CXCL2:

Chemokine-X-chemokine ligand 2

CNS:

Central nervous system

COX:

Cycloxygenase

DMT1:

Divalent metal transporter 1

DRD2:

Dopamine D2 receptor

EMR1:

Egf-like module containing mucin-like hormone receptor-like 1

FLISA:

Fluorescence-linked immunosorbent assay

GFAP:

Glial fibrillary acidic protein

GMA-MS:

Gas metal arc-mild steel

HO:

Heme-oxygenase

ICP-AES:

Inductive coupled plasma atomic absorption spectroscopy

IL6:

Interleukin 6

ITGAM:

Integrin αM

LDH:

Lactate dehydrogenase

MMA-HS:

Manual metal arc-hard surfacing

NOS:

Nitric oxide synthase

PCR:

Polymerase chain reaction

PD:

Parkinson’s disease

PMN:

Polymorphonuclear leukocyte

SDS:

Sodium dodecyl sulfate

TH:

Tyrosine hydroxylase

TNF:

Tumor necrosis factor

VMAT2:

Vesicular monoamine transporter 2

WF:

Welding fume

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The authors declare they have no proprietary, financial or personal interest of any kind or nature in any samples, products, supplies, service or company that could be construed as being a conflict of interest.

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  1. Health Effects Laboratory Division, National Institute For Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA

    Krishnan Sriram, Gary X. Lin, Amy M. Jefferson, Jenny R. Roberts, Rebecca S. Chapman, Bean T. Chen & James M. Antonini

  2. National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, 27711, USA

    Joleen M. Soukup & Andrew J. Ghio

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  1. Krishnan Sriram
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  2. Gary X. Lin
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Correspondence to Krishnan Sriram.

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Sriram, K., Lin, G.X., Jefferson, A.M. et al. Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes. Arch Toxicol 84, 521–540 (2010). https://doi.org/10.1007/s00204-010-0525-9

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