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  • 1
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    Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish (2019)
    Nature Research
    Details
    Publication Date: 2022-05-25
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brun, N. R., van Hage, P., Hunting, E. R., Haramis, A. G., Vink, S. C., Vijver, M. G., Schaaf, M. J. M., & Tudorache, C. Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish. Communications Biology, 2, (2019): 382, doi:10.1038/s42003-019-0629-6.
    Description: Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity.
    Description: We thank Natalia Novik and Laurie Mans for technical assistance during glucose assay and in situ hybridisation, respectively, Rubén Marín-Juez for providing the ins riboprobe, and John J. Stegeman for his helpful comments on the manuscript. The research described in this work was supported by the Dutch research council NWO (MGV; 864.13.010).
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 2
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    Nanoparticles induce dermal and intestinal innate immune system responses in zebrafish embryos (2018)
    Details
    Publication Date: 2022-05-25
    Description: Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Environmental Science: Nano 5 (2018):904-916, doi:10.1039/C8EN00002F.
    Description: Major molecular mechanisms that underpin the toxicity of nanoparticles (NPs) are the formation of reactive oxygen species and the induction of inflammation. The latter is frequently observed in vitro and in mammalian organisms, yet in aquatic organisms, such NP-induced inflammatory responses remain largely unexplored. Zebrafish offer a wide range of molecular tools to investigate immune responses in an aquatic organism, and were therefore used here to describe how copper (Cu) NPs (25 nm; 1 mg L-1) and soluble Cu as well as polystyrene (PS) NPs (25 nm; 10 mg L1-) induce innate immune responses, focussing on the skin cells and the intestine as likely organs of interaction. mRNA expression of the immune responsive genes interleukin 1 beta (il1β) and immunoresponsive gene 1-like (irg1l) of CuNP exposed embryos was observed to be 46 weaker in the intestinal tissue compared to the rest of the body, indicating a strong outer epithelium response. Specifically, NPs were observed to accumulate in the cavities of lateral neuromasts in the skin, which coincided with an increased local expression of il1β. Exposure to CuNPs triggered the strongest transcriptional changes in pro-inflammatory-related genes and was also observed to increase migration of neutrophils in the tail, indicating a NP-specific inflammatory response. This is the first in vivo evidence for waterborne NP exposure triggering alterations of immune system regulating genes in the skin and intestines of zebrafish embryos. The observed molecular responses have the potential to be linked to adverse effects at higher levels of biological organization and hence might offer screening purposes in nanotoxicology or building blocks for adverse outcome pathways.
    Description: This study was funded by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2014–655424) granted to Mónica Varela and the NWO-VIDI 864.13.010 granted to Martina G. Vijver.
    Keywords: Copper nanoparticles ; Polystyrene nanoparticles ; Inflammation ; Neuromasts ; Intestine
    Repository Name: Woods Hole Open Access Server
    Type: Preprint
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  • 3
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    Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish (2021)
    Nature Research
    Details
    Publication Date: 2022-05-27
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brun, N. R., Panlilio, J. M., Zhang, K., Zhao, Y., Ivashkin, E., Stegeman, J. J., & Goldstone, J. Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish. Communications Biology, 4(1), (2021): 1129, https://doi.org/10.1038/s42003-021-02626-9.
    Description: The most abundant polychlorinated biphenyl (PCB) congeners found in the environment and in humans are neurotoxic. This is of particular concern for early life stages because the exposure of the more vulnerable developing nervous system to neurotoxic chemicals can result in neurobehavioral disorders. In this study, we uncover currently unknown links between PCB target mechanisms and neurobehavioral deficits using zebrafish as a vertebrate model. We investigated the effects of the abundant non-dioxin-like (NDL) congener PCB153 on neuronal morphology and synaptic transmission linked to the proper execution of a sensorimotor response. Zebrafish that were exposed during development to concentrations similar to those found in human cord blood and PCB contaminated sites showed a delay in startle response. Morphological and biochemical data demonstrate that even though PCB153-induced swelling of afferent sensory neurons, the disruption of dopaminergic and GABAergic signaling appears to contribute to PCB-induced motor deficits. A similar delay was observed for other NDL congeners but not for the potent dioxin-like congener PCB126. The effects on important and broadly conserved signaling mechanisms in vertebrates suggest that NDL PCBs may contribute to neurodevelopmental abnormalities in humans and increased selection pressures in vertebrate wildlife.
    Description: This work was supported by the Swiss National Science Foundation P2EZP2_165200 (NRB), the Boston University Superfund Research Program NIH 5P42ES007381 (J.J.S. and J.V.G.), the Woods Hole Center for Oceans and Human Health (NIH: P01ES021923 and P01ES028938; NSF: OCE-1314642 and OCE-1840381) (N.R.B., J.M.P., and J.J.S.), and the National Natural Science Foundation of China 22006099 (K.Z. and Y.Z.) and the Shanghai Pujiang Program 19PJ1404900 (K.Z. and Y.Z.).
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 4
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    Orphan cytochrome P450 20a1 CRISPR/Cas9 mutants and neurobehavioral phenotypes in zebrafish (2022)
    Nature Research
    Details
    Publication Date: 2022-05-27
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brun, N. R., Salanga, M. C., Mora-Zamorano, F. X., Lamb, D. C., Goldstone, J. V., & Stegeman, J. J. Orphan cytochrome P450 20a1 CRISPR/Cas9 mutants and neurobehavioral phenotypes in zebrafish. Scientific Reports, 11(1), (2021): 23892, https://doi.org/10.1038/s41598-021-03068-3.
    Description: Orphan cytochrome P450 (CYP) enzymes are those for which biological substrates and function(s) are unknown. Cytochrome P450 20A1 (CYP20A1) is the last human orphan P450 enzyme, and orthologs occur as single genes in every vertebrate genome sequenced to date. The occurrence of high levels of CYP20A1 transcripts in human substantia nigra and hippocampus and abundant maternal transcripts in zebrafish eggs strongly suggest roles both in the brain and during early embryonic development. Patients with chromosome 2 microdeletions including CYP20A1 show hyperactivity and bouts of anxiety, among other conditions. Here, we created zebrafish cyp20a1 mutants using CRISPR/Cas9, providing vertebrate models with which to study the role of CYP20A1 in behavior and other neurodevelopmental functions. The homozygous cyp20a1 null mutants exhibited significant behavioral differences from wild-type zebrafish, both in larval and adult animals. Larval cyp20a1-/- mutants exhibited a strong increase in light-simulated movement (i.e., light–dark assay), which was interpreted as hyperactivity. Further, the larvae exhibited mild hypoactivity during the adaptation period of the optomotor assays. Adult cyp20a1 null fish showed a pronounced delay in adapting to new environments, which is consistent with an anxiety paradigm. Taken together with our earlier morpholino cyp20a1 knockdown results, the results described herein suggest that the orphan CYP20A1 has a neurophysiological role.
    Description: These studies were supported in part by the Boston University Superfund Research Program NIH 5P42ES007381 (MCS, NRB, FXM, JVG, JJS), the Woods Hole Center for Oceans and Human Health (NIH: P01ES021923 and P01ES028938; NSF: OCE-1314642 and OCE-1840381; NRB and JJS), and EBI/EMBL Medakatox NIEHS R01ES029917 (JVG). DCL was funded by a UK-US Fulbright Scholarship.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 5
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    Microbially-mediated indirect effects of silver nanoparticles on aquatic invertebrates (2018)
    Springer
    Details
    Publication Date: 2022-05-26
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Aquatic Sciences 80 (2018): 44, doi:10.1007/s00027-018-0594-z.
    Description: Complex natural systems are affected by multiple anthropogenic stressors, and therefore indirect effects within food webs are increasingly investigated. In this context, dead organic matter (OM) or detritus provides a food source sustaining detrital food webs that recycle the retained energy through microbial decomposition and invertebrate consumption. In aquatic environments, poorly water-soluble contaminants, including nanoparticles (NPs), quickly adsorb onto OM potentially modifying OM-associated microbial communities. Since invertebrates often depend on microbial conditioning to enhance OM quality, adverse effects on OM-associated microbial communities could potentially affect invertebrate performances. Therefore, this study assessed the effect of environmentally relevant concentrations of the model emerging contaminant, silver nanoparticles (AgNPs), on OM-associated microorganisms and subsequent indirect effects on growth of the invertebrate Asellus aquaticus. At low concentrations (0.8 ug/L), AgNPs inhibited activity and altered metabolic diversity of the OM-associated microbial community. This was observed to coincide with a negative effect on the growth of A. aquaticus due to antimicrobial properties, as a decreased growth was observed when offered AgNP-contaminated OM. When A. aquaticus were offered sterile OM in the absence of AgNPs, invertebrate growth was observed to be strongly retarded, illustrating the importance of microorganisms in the diet of this aquatic invertebrate. This outcome thus hints that environmentally relevant concentrations of AgNPs can indirectly affect the growth of aquatic invertebrates by affecting OM-associated microbial communities, and hence that microorganisms are an essential link in understanding bottom-up directed effects of chemical stressors in food webs.
    Description: The Chinese Scholarship Council (CSC) is gratefully acknowledged for its financial support to Yujia Zhai [201506510003]. Martina G. Vijver is funded by NWO-VIDI [project number 864.13.010].
    Keywords: Asellus aquaticus ; Food web ; Freshwater biofilms ; Decomposition and consumption ; Silver nanoparticles ; Ecosystem functioning
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 6
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    Transcriptome responses in polar cod (Boreogadus saida) liver slice culture exposed to benzo[a]pyrene and ethynylestradiol: insights into anti-estrogenic effects (2021)
    Elsevier
    Details
    Publication Date: 2022-05-27
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Yadetie, F., Brun, N. R., Vieweg, I., Nahrgang, J., Karlsen, O. A., & Goksoyr, A. Transcriptome responses in polar cod (Boreogadus saida) liver slice culture exposed to benzo[a]pyrene and ethynylestradiol: insights into anti-estrogenic effects. Toxicology in Vitro, 75, (2021): 105193 https://doi.org/10.1016/j.tiv.2021.105193.
    Description: Polar cod (Boreogadus saida) is a key species in the arctic marine ecosystem vulnerable to effects of pollution, particularly from petroleum related activities. To facilitate studying the effects of those pollutants, we adapted a precision-cut liver slice culture protocol for this species. Using this system on board a research vessel, we studied gene expression in liver slice after exposure to the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP), ethynylestradiol (EE2), and their mixtures, to map their molecular targets and examine possible anti-estrogenic effects of BaP. The exposure experiments were performed with BaP alone (0.1, 1, and 10 μM) or in combination with low concentrations of EE2 (5 nM) to mimic physiological estradiol levels in early vitellogenic female fish. Transcriptome analysis (RNA-seq) was performed after 72 h exposure in culture to map the genes and cellular pathways affected. The results provide a view of global transcriptome responses to BaP and EE2, which resulted in enrichment of many pathways such as the aryl hydrocarbon (Ahr) and estrogen receptor pathways. In the mixture exposure, BaP resulted in anti-estrogenic effects, shown by attenuation of EE2 activated transcription of many estrogen target genes. The results from this ex vivo experiment suggest that pollutants that activate the Ahr pathway such as the PAH compound BaP can result in anti-estrogenic effects that may lead to endocrine disruption in polar cod.
    Description: The study was funded by the Research Council of Norway, projects Nansen Legacy (276730), dCod 1.0 (248840), and the iCod 2.0 (244564).
    Keywords: Ahr ; ER ; Polar cod ; Liver ; PAH ; Anti-estrogen
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 7
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    Resistance to Cyp3a induction by polychlorinated biphenyls, including non-dioxin-like PCB153, in gills of killifish (Fundulus heteroclitus) from New Bedford Harbor (2021)
    Elsevier
    Details
    Publication Date: 2022-05-26
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Celander, M. C., Goldstone, J. V., Brun, N. R., Clark, B., Jayaraman, S., Nacci, D., & Stegeman, J. J. Resistance to Cyp3a induction by polychlorinated biphenyls, including non-dioxin-like PCB153, in gills of killifish (Fundulus heteroclitus) from New Bedford Harbor. Environmental Toxicology and Pharmacology, 83, (2021): 103580. doi: 10.1016/j.etap.2020.103580.
    Description: Previous reports suggested that non-dioxin-like (NDL) PCB153 effects on cytochrome P450 3A (Cyp3a) expression in Atlantic killifish (Fundulus heteroclitus) gills differed between F0 generation fish from a PCB site (New Bedford Harbor; NBH) and a reference site (Scorton Creek; SC). Here, we examined effects of PCB153, dioxin-like (DL) PCB126, or a mixture of both, on Cyp3a56 mRNA in killifish generations removed from the wild, without environmental PCB exposures. PCB126 effects in liver and gills differed between populations, as expected. Gill Cyp3a56 was not affected by either congener in NBH F2 generation fish, but was induced by PCB153 in SC F1 fish, with females showing a greater response. PCB153 did not affect Cyp3a56 in liver of either population. Results suggest a heritable resistance to NDL-PCBs in killifish from NBH, in addition to that reported for DL PCBs. Induction of Cyp3a56 in gills may be a biomarker of exposure to NDL PCBs in fish populations that are not resistant to PCBs.
    Description: This study was supported by the sabbatical program from the Faculty of Science at the University of Gothenburg (MC), and by the Swiss National Science Foundation P2EZP2-165200 (NRB). The study was supported in part by the Superfund Hazardous Substances Research Program at Boston University NIH P42ES007381 (JVG, JJS). This research was also funded partly by the US Environmental Protection Agency (SJ, DN), including an appointment (BC) with the Postdoctoral Research Program at the US Environmental Protection (US-EPA) Office of Research and Development administered by the Oak Ridge Institute for Science and Education (ORISE), through Interagency Agreement No. DW92429801 between the US Department of Energy and the US-EPA. The contents do not reflect the views of the US-EPA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use by the US-EPA. We thank Rene Francolini at the Woods Hole Oceanographic Institutions for excellent technical assistance and Dr. Sibel Karchner and Dr. Mark Hahn at the Woods Hole Oceanographic Institutions for valuable discussions and comments on the manuscript.
    Keywords: PCB153 ; Fish ; Gills ; Cyp3a ; Resistance
    Repository Name: Woods Hole Open Access Server
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