@misc{BaeslerMichaelisStibolleretal.2021,
  author    = {Baesler, Jessica and Michaelis, Vivien and Stiboller, Michael and Haase, Hajo and Aschner, Michael and Schwerdtle, Tanja and Sturzenbaum, Stephen R. and Bornhorst, Julia},
  title     = {Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {8},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-51499},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-514995},
  pages     = {13},
  year      = {2021},
  abstract  = {Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.},
  language  = {en}
}
@article{NicolaiBaeslerAschneretal.2020,
  author    = {Nicolai, Merle Marie and Baesler, Jessica and Aschner, Michael and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Consequences of manganese overload in C. elegans},
  series = {Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft f{\"u}r Experimentelle und Klinische Pharmakologie und Toxikologie},
  volume    = {393},
  journal   = {Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft f{\"u}r Experimentelle und Klinische Pharmakologie und Toxikologie},
  number    = {SUPPL 1},
  publisher = {Springer},
  address   = {New York},
  issn      = {0028-1298},
  doi       = {10.1007/s00210-020-01828-y},
  pages     = {9 -- 9},
  year      = {2020},
  language  = {en}
}
@article{ChenBornhorstAschner2018,
  author    = {Chen, Pan and Bornhorst, Julia and Aschner, Michael},
  title     = {Manganese metabolism in humans},
  series = {Frontiers in Bioscience-Landmark},
  volume    = {23},
  journal   = {Frontiers in Bioscience-Landmark},
  number    = {9},
  publisher = {Frontiers in Bioscience INC},
  address   = {Irvine},
  issn      = {1093-9946},
  doi       = {10.2741/4665},
  pages     = {1655 -- 1679},
  year      = {2018},
  abstract  = {Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.},
  language  = {en}
}
@article{FerrerPeresdosSantosetal.2018,
  author    = {Ferrer, Beatriz and Peres, Tanara Vieira and dos Santos, Alessandra Antunes and Bornhorst, Julia and Morcillo, Patricia and Goncalves, Cinara Ludvig and Aschner, Michael},
  title     = {Methylmercury affects the expression of hypothalamic neuropeptides that control body weight in C57BL/6J mice},
  series = {Toxicological sciences},
  volume    = {163},
  journal   = {Toxicological sciences},
  number    = {2},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1096-6080},
  doi       = {10.1093/toxsci/kfy052},
  pages     = {557 -- 568},
  year      = {2018},
  abstract  = {Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 mu M). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agouti-related peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender-and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.},
  language  = {en}
}
@article{RohnMarschallKroepfletal.2018,
  author    = {Rohn, Isabelle and Marschall, Talke Anu and Kr{\"o}pfl, Nina and Jensen, Kenneth Bendix and Aschner, Michael and Tuck, Simon and Kuehnelt, Doris and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Selenium species-dependent toxicity, bioavailability and metabolic transformations in Caenorhabditis elegans},
  series = {Metallomics : integrated biometal science},
  volume    = {10},
  journal   = {Metallomics : integrated biometal science},
  number    = {6},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c8mt00066b},
  pages     = {818 -- 827},
  year      = {2018},
  abstract  = {The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys). An inverse relationship was found between toxicity and bioavailability of the Se species, with the organic species displaying a higher bioavailability than the inorganic form, yet being less toxic. Quantitative Se speciation analysis with HPLC/mass spectrometry revealed a partial metabolism of SeMet and MeSeCys. In SeMet exposed worms, identified metabolites were Se-adenosylselenomethionine (AdoSeMet) and Se-adenosylselenohomocysteine (AdoSeHcy), while worms exposed to MeSeCys produced Se-methylselenoglutathione (MeSeGSH) and -glutamyl-MeSeCys (-Glu-MeSeCys). Moreover, the possible role of the sole selenoprotein in the nematode, thioredoxin reductase-1 (TrxR-1), was studied comparing wildtype and trxr-1 deletion mutants. Although a lower basal Se level was detected in trxr-1 mutants, Se toxicity and bioavailability following acute exposure was indistinguishable from wildtype worms. Altogether, the current study demonstrates the suitability of C. elegans as a model for Se species dependent toxicity and metabolism, while further research is needed to elucidate TrxR-1 function in the nematode.},
  language  = {en}
}
@article{GubertPuntelLehmenetal.2018,
  author    = {Gubert, Priscila and Puntel, Bruna and Lehmen, Tassia and Fessel, Joshua P. and Cheng, Pan and Bornhorst, Julia and Trindade, Lucas Siqueira and Avila, Daiana S. and Aschner, Michael and Soares, Felix A. A.},
  title     = {Metabolic effects of manganese in the nematode Caenorhabditis elegans through DAergic pathway and transcription factors activation},
  series = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system},
  volume    = {67},
  journal   = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0161-813X},
  doi       = {10.1016/j.neuro.2018.04.008},
  pages     = {65 -- 72},
  year      = {2018},
  abstract  = {Manganese (Mn) is an essential trace element for physiological functions since it acts as an enzymatic co-factor. Nevertheless, overexposure to Mn has been associated with a pathologic condition called manganism. Furthermore, Mn has been reported to affect lipid metabolism by mechanisms which have yet to be established. Herein, we used the nematode Caenorhabditis elegans to examine Mn's effects on the dopaminergic (DAergic) system and determine which transcription factors that regulate with lipid metabolism are affected by it. Worms were exposed to Mn for four hours in the presence of bacteria and in a liquid medium (85 mM NaCl). Mn increased fat storage as evidenced both by Oil Red O accumulation and triglyceride levels. In addition, metabolic activity was reduced as a reflection of decreased oxygen consumption caused by Mn. Mn also affected feeding behavior as evidenced by decreased pharyngeal pumping rate. DAergic neurons viability were not altered by Mn, however the dopamine levels were significantly reduced following Mn exposure. Furthermore, the expression of sbp-1 transcription factor and let-363 protein kinase responsible for lipid accumulation control was increased and decreased, respectively, by Mn. Altogether, our data suggest that Mn increases the fat storage in C. elegans, secondary to DAergic system alterations, under the control of SBP-1 and LET-363 proteins.},
  language  = {en}
}
@misc{NicolaiWeishauptBaesleretal.2021,
  author    = {Nicolai, Merle Marie and Weishaupt, Ann-Kathrin and Baesler, Jessica and Brinkmann, Vanessa and Wellenberg, Anna and Winkelbeiner, Nicola Lisa and Gremme, Anna and Aschner, Michael and Fritz, Gerhard and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Effects of manganese on genomic integrity in the multicellular model organism Caenorhabditis elegans},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1173},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-52327},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-523275},
  pages     = {18},
  year      = {2021},
  abstract  = {Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms.},
  language  = {en}
}
@article{NicolaiWeishauptBaesleretal.2021,
  author    = {Nicolai, Merle Marie and Weishaupt, Ann-Kathrin and Baesler, Jessica and Brinkmann, Vanessa and Wellenberg, Anna and Winkelbeiner, Nicola Lisa and Gremme, Anna and Aschner, Michael and Fritz, Gerhard and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Effects of manganese on genomic integrity in the multicellular model organism Caenorhabditis elegans},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms222010905},
  pages     = {16},
  year      = {2021},
  abstract  = {Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms.},
  language  = {en}
}
@article{RuszkiewiczdeMacedoMirandaVizueteetal.2018,
  author    = {Ruszkiewicz, Joanna A. and de Macedo, Gabriel Teixeira and Miranda-Vizuete, Antonio and Teixeira da Rocha, Joao B. and Bowman, Aaron B. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael},
  title     = {The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner},
  series = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system},
  volume    = {68},
  journal   = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0161-813X},
  doi       = {10.1016/j.neuro.2018.08.007},
  pages     = {189 -- 202},
  year      = {2018},
  abstract  = {Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans.},
  language  = {en}
}
@article{PeresArantesMiahetal.2018,
  author    = {Peres, Tanara Vieira and Arantes, Leticia P. and Miah, Mahfuzur R. and Bornhorst, Julia and Schwerdtle, Tanja and Bowman, Aaron B. and Leal, Rodrigo B. and Aschner, Michael},
  title     = {Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity},
  series = {Neurotoxicity Research},
  volume    = {34},
  journal   = {Neurotoxicity Research},
  number    = {3},
  publisher = {Springer},
  address   = {New York},
  issn      = {1029-8428},
  doi       = {10.1007/s12640-018-9915-1},
  pages     = {584 -- 596},
  year      = {2018},
  abstract  = {Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.},
  language  = {en}
}
@article{BornhorstEbertMeyeretal.2020,
  author    = {Bornhorst, Julia and Ebert, Franziska and Meyer, S{\"o}ren and Ziemann, Vanessa and Xiong, Chan and Guttenberger, Nikolaus and Raab, Andrea and Baesler, Jessica and Aschner, Michael and Feldmann, J{\"o}rg and Francesconi, Kevin and Raber, Georg and Schwerdtle, Tanja},
  title     = {Toxicity of three types of arsenolipids},
  series = {Metallomics},
  volume    = {12},
  journal   = {Metallomics},
  number    = {5},
  publisher = {Oxford University Press},
  address   = {Cambridge},
  issn      = {1756-591X},
  doi       = {https://doi.org/10.1039/d0mt00039f},
  pages     = {794 -- 798},
  year      = {2020},
  abstract  = {Although fish and seafood are well known for their nutritional benefits, they contain contaminants that might affect human health. Organic lipid-soluble arsenic species, so called arsenolipids, belong to the emerging contaminants in these food items; their toxicity has yet to be systematically studied. Here, we apply the in vivo model Caenorhabditis elegans to assess the effects of two arsenic-containing hydrocarbons (AsHC), a saturated arsenic-containing fatty acid (AsFA), and an arsenic-containing triacylglyceride (AsTAG) in a whole organism. Although all arsenolipids were highly bioavailable in Caenorhabditis elegans, only the AsHCs were substantially metabolized to thioxylated or shortened metabolic products and induced significant toxicity, affecting both survival and development. Furthermore, the AsHCs were several fold more potent as compared to the toxic reference arsenite. This study clearly indicates the need for a full hazard identification of subclasses of arsenolipids to assess whether they pose a risk to human health.},
  language  = {en}
}
@article{BaeslerMichaelisStibolleretal.2021,
  author    = {Baesler, Jessica and Michaelis, Vivien and Stiboller, Michael and Haase, Hajo and Aschner, Michael and Schwerdtle, Tanja and Sturzenbaum, Stephen R. and Bornhorst, Julia},
  title     = {Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis},
  series = {Molecular Nutrition and Food Research},
  volume    = {65},
  journal   = {Molecular Nutrition and Food Research},
  number    = {8},
  publisher = {Wiley-VCH GmbH},
  address   = {Weinheim},
  issn      = {1613-4133},
  doi       = {10.1002/mnfr.202001176},
  pages     = {1 -- 11},
  year      = {2021},
  abstract  = {Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.},
  language  = {en}
}
@article{BaeslerKoppPohletal.2019,
  author    = {Baesler, Jessica and Kopp, Johannes Florian and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans},
  series = {Journal of Trace Elements in Medicine and Biology},
  volume    = {55},
  journal   = {Journal of Trace Elements in Medicine and Biology},
  publisher = {Elsevier},
  address   = {M{\"u}nchen},
  doi       = {10.1016/j.jtemb.2019.05.005},
  pages     = {44 -- 49},
  year      = {2019},
  abstract  = {While the underlying mechanisms of Parkinson's disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.},
  language  = {en}
}
@article{RuszkiewiczdeMacedoMirandaVizueteetal.2019,
  author    = {Ruszkiewicz, Joanna A. and de Macedo, Gabriel Teixeira and Miranda-Vizuete, Antonio and Bowman, Aaron B. and Bornhorst, Julia and Schwerdtle, Tanja and Antunes Soares, Felix A. and Aschner, Michael},
  title     = {Sex-Specific response of caenorhabditis elegans to Methylmercury Toxicity},
  series = {Neurotoxicity Research},
  volume    = {35},
  journal   = {Neurotoxicity Research},
  number    = {1},
  publisher = {Springer},
  address   = {New York},
  issn      = {1029-8428},
  doi       = {10.1007/s12640-018-9949-4},
  pages     = {208 -- 216},
  year      = {2019},
  abstract  = {Methylmercury (MeHg), an abundant environmental pollutant, has long been known to adversely affect neurodevelopment in both animals and humans. Several reports from epidemiological studies, as well as experimental data indicate sex-specific susceptibility to this neurotoxicant; however, the molecular bases of this process are still not clear. In the present study, we used Caenorhabditis elegans (C. elegans), to investigate sex differences in response to MeHg toxicity during development. Worms at different developmental stage (L1, L4, and adult) were treated with MeHg for 1h. Lethality assays revealed that male worms exhibited significantly higher resistance to MeHg than hermaphrodites, when at L4 stage or adults. However, the number of worms with degenerated neurons was unaffected by MeHg, both in males and hermaphrodites. Lower susceptibility of males was not related to changes in mercury (Hg) accumulation, which was analogous for both wild-type (wt) and male-rich him-8 strain. Total glutathione (GSH) levels decreased upon MeHg in him-8, but not in wt. Moreover, the sex-dependent response of the cytoplasmic thioredoxin system was observedmales exhibited significantly higher expression of thioredoxin TRX-1, and thioredoxin reductase TRXR-1 expression was downregulated upon MeHg treatment only in hermaphrodites. These outcomes indicate that the redox status is an important contributor to sex-specific sensitivity to MeHg in C. elegans.},
  language  = {en}
}
@article{PeresHorningBornhorstetal.2019,
  author    = {Peres, Tanara V. and Horning, Kyle J. and Bornhorst, Julia and Schwerdtle, Tanja and Bowman, Aaron B. and Aschner, Michael},
  title     = {Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo},
  series = {Biological Trace Element Research},
  volume    = {188},
  journal   = {Biological Trace Element Research},
  number    = {1},
  publisher = {Human press inc.},
  address   = {Totowa},
  issn      = {0163-4984},
  doi       = {10.1007/s12011-018-1531-7},
  pages     = {127 -- 134},
  year      = {2019},
  abstract  = {Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric disturbances and may arise from an impaired or not fully developed excretion system, transporter malfunction and/or exposure to excessive levels of Mn. Therefore, deciphering processes regulating neuronal Mn homeostasis is essential to understand the mechanisms of Mn neurotoxicity. In the present study, we selected two small molecules (with opposing effects on Mn transport) from a previous high throughput screen of 40,167 to test their effects on Mn toxicity parameters in vivo using Caenorhabditis elegans. We pre-exposed worms to VU0063088 and VU0026921 for 30min followed by co-exposure for 1h with Mn and evaluated Mn accumulation, dopaminergic (DAergic) degeneration and worm survival. Control worms were exposed to vehicle (DMSO) and saline only. In pdat-1::GFP worms, with GFP labeled DAergic neurons, we observed a decrease of Mn-induced DAergic degeneration in the presence of both small molecules. This effect was also observed in an smf-2 knockout strain. SMF-2 is a regulator of Mn transport in the worms and this strain accumulates higher Mn levels. We did not observe improved survival in the presence of small molecules. Our results suggest that both VU0063088 and VU0026921 may modulate Mn levels in the worms through a mechanism that does not require SMF-2 and induce protection against Mn neurotoxicity.},
  language  = {en}
}
@article{RohnRaschkeAschneretal.2019,
  author    = {Rohn, Isabelle and Raschke, Stefanie and Aschner, Michael and Tuck, Simon and Kuehnelt, Doris and Kipp, Anna Patricia and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Treatment of caenorhabditis elegans with small selenium species enhances antioxidant defense systems},
  series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  volume    = {63},
  journal   = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  number    = {9},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.201801304},
  pages     = {9},
  year      = {2019},
  abstract  = {ScopeSmall selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo. Methods and resultsIn the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data. ConclusionSe species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake.},
  language  = {en}
}
@article{RohnKroepflAschneretal.2019,
  author    = {Rohn, Isabelle and Kroepfl, Nina and Aschner, Michael and Bornhorst, Julia and Kuehnelt, Doris and Schwerdtle, Tanja},
  title     = {Selenoneine ameliorates peroxide-induced oxidative stress in C. elegans},
  series = {Journal of trace elements in medicine and biology},
  volume    = {55},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier GMBH},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2019.05.012},
  pages     = {78 -- 81},
  year      = {2019},
  abstract  = {Scope: Selenoneine (2-selenyl-N-alpha, N-alpha, N-alpha-trimethyl-L-histidine), the selenium (Se) analogue of the ubiquitous thiol compound and putative antioxidant ergothioneine, is the major organic selenium species in several marine fish species. Although its antioxidant efficacy has been proposed, selenoneine has been poorly characterized, preventing conclusions on its possible beneficial health effects. Methods and results: Treatment of Caenorhabditis elegans (C. elegans) with selenoneine for 18 h attenuated the induction of reactive oxygen and nitrogen species (RONS). However, the effect was not immediate, occurring 48 h post-treatment. Total Se and Se speciation analysis revealed that selenoneine was efficiently taken up and present in its original form directly after treatment, with no metabolic transformations observed. 48 h posttreatment, total Se in worms was slightly higher compared to controls and no selenoneine could be detected. Conclusion: The protective effect of selenoneine may not be attributed to the presence of the compound itself, but rather to the activation of molecular mechanisms with consequences at more protracted time points.},
  language  = {en}
}
@article{BaeslerKoppPohletal.2019,
  author    = {Baesler, Jessica and Kopp, Johannes F. and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans},
  series = {Journal of trace elements in medicine and biology},
  volume    = {55},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier GMBH},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2019.05.005},
  pages     = {44 -- 49},
  year      = {2019},
  language  = {en}
}