@misc{BornhorstKippHaaseetal.2018, author = {Bornhorst, Julia and Kipp, Anna P. and Haase, Hajo and Meyer, Soeren and Schwerdtle, Tanja}, title = {The crux of inept biomarkers for risks and benefits of trace elements}, series = {Trends in Analytical Chemistry}, volume = {104}, journal = {Trends in Analytical Chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0165-9936}, doi = {10.1016/j.trac.2017.11.007}, pages = {183 -- 190}, year = {2018}, abstract = {Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE.}, 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{NicolaiWittFrieseetal.2022, author = {Nicolai, Merle Marie and Witt, Barbara and Friese, Sharleen and Michaelis, Vivien and H{\"o}lz-Armstrong, Lisa and Martin, Maximilian and Ebert, Franziska and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells}, series = {Food and chemical toxicology}, volume = {161}, journal = {Food and chemical toxicology}, publisher = {Elsevier}, address = {Oxford}, issn = {0278-6915}, doi = {10.1016/j.fct.2022.112822}, pages = {10}, year = {2022}, abstract = {Manganese (Mn) is an essential trace element, but overexposure is associated with toxicity and neurological dysfunction. Accumulation of Mn can be observed in dopamine-rich regions of the brain in vivo and Mn-induced oxidative stress has been discussed extensively. Nevertheless, Mn-induced DNA damage, adverse effects of DNA repair, and possible resulting consequences for the neurite network are not yet characterized. For this, LUHMES cells were used, as they differentiate into dopaminergic-like neurons and form extensive neurite networks. Experiments were conducted to analyze Mn bioavailability and cytotoxicity of MnCl2, indicating a dose-dependent uptake and substantial cytotoxic effects. DNA damage, analyzed by means of 8-oxo-7,8-dihydro-2'-guanine (8oxodG) and single DNA strand break formation, showed significant dose- and time-dependent increase of DNA damage upon 48 h Mn exposure. Furthermore, the DNA damage response was increased which was assessed by analytical quantification of poly(ADP-ribosyl)ation (PARylation). Gene expression of the respective DNA repair genes was not significantly affected. Degradation of the neuronal network is significantly altered by 48 h Mn exposure. Altogether, this study contributes to the characterization of Mn-induced neurotoxicity, by analyzing the adverse effects of Mn on genome integrity in dopaminergic-like neurons and respective outcomes.}, language = {en} } @article{PeresEyngLopesetal.2015, author = {Peres, Tanara V. and Eyng, Helena and Lopes, Samantha C. and Colle, Dirleise and Goncalves, Filipe M. and Venske, Debora K. R. and Lopes, Mark W. and Ben, Juliana and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and Farina, Marcelo and Prediger, Rui D. and Leal, Rodrigo B.}, title = {Developmental exposure to manganese induces lasting motor and cognitive impairment in rats}, series = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, volume = {50}, 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.2015.07.005}, pages = {28 -- 37}, year = {2015}, abstract = {Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum. (C) 2015 Elsevier Inc. All rights reserved.}, language = {en} }