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Welding fume-related dopaminergic neurotoxicity.
Sriram-K; Lin-GX; Jefferson-AM; Wirth-O; Hayashi-Y; Roberts-JR; Chapman-RS; Krajnak-KM; Antonini-JM
Parkinsonism Relat Disord 2009 Dec; 15(Supple 2):S162
Manganese (Mn) intoxication is associated with increased prevalence of neurological conditions resembling Parkinson's disease (PD). The presence of Mn in welding consumables therefore raises concerns about potential neurological risks following occupational exposure to welding fume (WF). To investigate if WF exposure induces neurotoxicity, we treated rats with low- and high-Mn containing WF. Repeated intratracheal instillations (0.5 mg/rat, 1/wk × 7wks) of gas metal arc-mild steel (GMA-MS; low Mn, insoluble) or manual metal arc-hard surfacing (MMA-HS; high Mn, soluble) fumes caused loss of tyrosine hydroxylase (TH) protein in the striatum (-20%) and midbrain (-30%) by 1 d post-exposure. While loss of TH following GMA-MS was transient, a sustained loss was observed in the midbrain (34%) even after cessation of MMA-HS exposure. Both fumes caused down-regulation of D2 receptor (30-40%) and Vmat2 (30-55%) mRNAs in the midbrain. A different exposure paradigm (2 mg/rat, 1/wk × 28 wks) resulted in loss of Park 5 and Park 7 proteins in striatum (40-50%), but not midbrain. A similar regimen of MnCl2 caused extensive loss of these proteins in both striatum (70-80%) and midbrain (60%). All treated animals exhibited hyperactivity but not deficits in gross-motor behavior. As mutations in PARK genes have been linked to onset of PD and because welding is implicated as a risk factor for idiopathic PD, it remains to be elucidated if PARK genes have an underlying role in the pathogenesis of WF-induced neurodegeneration. Our findings suggest that Mn-containing WF can cause persistent alteration of several PD-related genes that could lead to dopaminergic neurodegeneration.
Manganese-compounds; Neurological-diseases; Neurological-system; Welders; Welding-industry; Welding; Neurotoxic-effects; Laboratory-animals; Animal-studies; Central-nervous-system; Central-nervous-system-disorders
Parkinsonism & Related Disorders. Abstracts of the WFN IVIII World Congress of Parkinson's Disease and Related Disorders, December 13-16, 2009, Miami Beach, FL, USA