Parkinson's disease (PD) is a neurodegenerative brain disorder characterized by selective dopaminergic (DAergic) cell loss that results in overt motor and cognitive deficits. Current treatment options exist to combat PD symptomatology, but are unable to directly target its pathogenesis due to a lack of knowledge concerning its etiology. Several genes have been linked to PD, including three genes associated with an early-onset familial form: parkin, pink1 and dj1. All three genes are implicated in regulating oxidative stress pathways. Another hallmark of PD pathophysiology is Lewy body deposition, associated with the gain-of-function genetic risk factor α-synuclein. The function of α-synuclein is poorly understood, as it shows both neurotoxic and neuroprotective activities in PD. Using the genetically tractable invertebrate Caenorhabditis elegans (C. elegans) model system, the neurotoxic or neuroprotective role of α-synuclein upon acute Mn exposure in the background of mutated pdr1, pink1 or djr1.1 was examined. The pdr1 and djr1.1 mutants showed enhanced Mn accumulation and oxidative stress that was rescued by α-synuclein. Moreover, DAergic neurodegeneration, while unchanged with Mn exposure, returned to wild-type (WT) levels for pdr1, but not djr1.1 mutants expressing α-synuclein. Taken together, this study uncovers a novel, neuroprotective role for WT human α-synuclein in attenuating Mn-induced toxicity in the background of PD-associated genes, and further supports the role of extracellular dopamine in exacerbating Mn neurotoxicity.

A new method for elemental bioimaging with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to study the uptake of manganese (Mn) in Caenorhabditis elegans (C. elegans). C. elegans is a well-established model organism in neuroscience, genetics and genomics, which has been extensively studied to decipher mechanisms of heavy metal induced toxicity. Knowledge about the distribution of manganese (Mn) and other metals in this organism will be helpful in elucidating pathways and mechanisms of transport, distribution and excretion. The LA-ICP-MS method requires limited sample preparation and can be used rapidly and easily to visualize the Mn distribution in C. elegans. Due to thorough optimization of the analytical parameters, intense Mn signals in C. elegans wild-type (WT) and mutants were obtained at a spatial resolution as small as 4 μm, thus proving the suitability of LA-ICP-MS to study the uptake of metals in C. elegans.

Due to several polycyclic aromatic hydrocarbons (PAHs) being highly carcinogenic and at the same time occurring at very low environmental concentrations up to the microgram per kilogram range, highly sensitive chemical analysis in various matrices is needed. Here, for the first time, a method using gas chromatography (GC) and atmospheric pressure laser ionization-mass spectrometry (APLI-MS), which is much more sensitive compared to common GC-MS, proved to produce reliable (certified reference materials) and comparable (GC-MS) results. PAHs and selected isomers of alkyl-PAHs were targeted, whereby 53 analytes could be quantified individually; for one pair, the sum had to be calculated. In combination with the selective and sensitive (1+1)-REMPI process of the APLI, limits of detection (LODs) between 5 and 50 fg/μL could be obtained. To prove the reliability of this method, four certified reference materials (SRM1649b urban dust, SRM 1941b organics in marine sediment, BCR 535 fresh water harbor sediment, and ERM CC013a contaminated soil from a former gas plant site) were analyzed. The results were in good accordance with the certified values. In addition, analytical results of three different environmental matrices (bituminous coal, suspended particulate matter from river and pine needles) were compared to values obtained with well-established GC-EI-MS. The results show that this method presents an excellent tool ready-to-use for the analysis of environmental samples with very low PAH content or very low sample amount.

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