@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}
}
@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}
}
@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{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{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{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{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}
}
@article{IjomoneIroegbuMorcilloetal.2022,
  author    = {Ijomone, Omamuyovwi M. and Iroegbu, Joy D. and Morcillo, Patricia and Ayodele, Akinyemi J. and Ijomone, Olayemi K. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael},
  title     = {Sex-dependent metal accumulation and immunoexpression of Hsp70 and Nrf2 in rats' brain following manganese exposure},
  series = {Environmental toxicology},
  volume    = {37},
  journal   = {Environmental toxicology},
  number    = {9},
  publisher = {Wiley},
  address   = {New York, NY},
  issn      = {1520-4081},
  doi       = {10.1002/tox.23583},
  pages     = {2167 -- 2177},
  year      = {2022},
  abstract  = {Manganese (Mn), although important for multiple cellular processes, has posed environmental health concerns due to its neurotoxic effects. In recent years, there have been extensive studies on the mechanism of Mn-induced neuropathology, as well as the sex-dependent vulnerability to its neurotoxic effects. Nonetheless, cellular mechanisms influenced by sex differences in susceptibility to Mn have yet to be adequately characterized. Since oxidative stress is a key mechanism of Mn neurotoxicity, here, we have probed Hsp70 and Nrf2 proteins to investigate the sex-dependent changes following exposure to Mn. Male and female rats were administered intraperitoneal injections of MnCl2 (10 mg/kg and 25 mg/kg) 48 hourly for a total of eight injections (15 days). We evaluated changes in body weight, as well as Mn accumulation, Nrf2 and Hsp70 expression across four brain regions; striatum, cortex, hippocampus and cerebellum in both sexes. Our results showed sex-specific changes in body-weight, specifically in males but not in females. Additionally, we noted sex-dependent accumulation of Mn in the brain, as well as in expression levels of Nrf2 and Hsp70 proteins. These findings revealed sex-dependent susceptibility to Mn-induced neurotoxicity corresponding to differential Mn accumulation, and expression of Hsp70 and Nrf2 across several brain regions.},
  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}
}