摘要：Although manganese (Mn) is an essential trace element, concerns are rising about the neurotoxic effects of elevated Mn exposure (environmental and occupational) in humans. Mn overexposure promotes a neuropathy resembling Parkinson׳s disease (PD). While only 10–20% of PD cases are documented as having genetic causes, growing evidence implicates an environmental/occupational contribution. Therefore, by using the genetically amenable Caenorhabditis elegans (C. elegans) model system, interactions between Mn and the two PD associated genes (dj-1.1 and pink1) were studied to address the question: is Mn toxicity and dopaminergic (DA) neurodegeneration exacerbated in djr-1.1 or pink1 deletion mutants? Worms with a djr-1.1 deletion (tm918) or pink1 deletion (tm1779), genes that both regulate oxidative stress pathways, were utilised. The genetic deletion of either gene did not increase mortality in L1 worms acutely exposed to Mn, with an LD50 indistinguishable from wildtype (WT) worms. However, djr-1.1 and pink1 deletion mutants exhibited altered oxidative defence responses compared to WT worms, as confirmed by inherently decreased total glutathione (GSH) levels and increased Mn-induced reactive oxygen/nitrogen species (RONS) induction. Interestingly, the djr-1.1 deletion mutants showed a quicker and more robust increase in RONS induction compared to WT and pink1 deletion mutants upon exposure to Mn. This effect correlated with increased Mn bioavailability in the djr-1.1 deletion mutants compared to WT and pink1 worms, as confirmed by ICP-MS/MS and LA-ICP-MS.
