RGD Reference Report - Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes. - Rat Genome Database

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Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes.

Authors: Sriram, K  Lin, GX  Jefferson, AM  Roberts, JR  Chapman, RS  Chen, BT  Soukup, JM  Ghio, AJ  Antonini, JM 
Citation: Sriram K, etal., Arch Toxicol. 2010 Jul;84(7):521-40. Epub 2010 Mar 12.
RGD ID: 5130952
Pubmed: PMID:20224926   (View Abstract at PubMed)
DOI: DOI:10.1007/s00204-010-0525-9   (Journal Full-text)

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 x 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.




Biological Process

  
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Original Reference(s)
Slc18a2Ratresponse to metal ion  IEP welding fumes Mn more ...RGD 
ThRatresponse to metal ion  IEP welding fumes Mn more ...RGD 


Genes (Rattus norvegicus)
Slc18a2  (solute carrier family 18 member A2) Th  (tyrosine hydroxylase)