Metal-induced neurodegeneration in C. elegans

Chen, Pan; Martinez-Finley, Ebany J.; Bornhorst, Julia; Chakraborty, Sudipta; Aschner, Michael

doi:10.3389/fnagi.2013.00018

Cited by 65 publications

(60 citation statements)

References 142 publications

(200 reference statements)

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“…Although the toxic effects of CuO NPs on nematodes has not been extensively studied [15], copper ions from copper salts have been shown to be toxic to several species, including C . elegans [16], Panagrellus redivivus , and Pristionchus pacificus [17]. Exposure of laboratory-adapted C .…”

Section: Introductionmentioning

confidence: 99%

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Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

et al. 2016

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Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress).

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Section: Introductionmentioning

confidence: 99%

“…elegans is an excellent model to study neuronal health as it offers a relatively simple nervous system [16]. This use has been exploited to study neurodegeneration induced by metals [16,20,33]. Neurodegeneration is a sensitive toxicological endpoint of copper ion exposure [34].…”

Section: Introductionmentioning

confidence: 99%

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

et al. 2016

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“…A single hermaphrodite has the ability to produce approximately 300 offspring, which enables high-throughput analyses 27 . C. elegans is less complex than the mammalian system, while still sharing high genetic homology (60–80%) 28 . The model organism C. elegans has been previously used in a limited number of studies to identify interactions between Cisplatin and signaling pathways in vivo 29–31 .…”

Section: Introductionmentioning

confidence: 99%

Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS

et al. 2015

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Cis-diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 µm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.

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“…(Zhao et al, 2014) Ferritin up-regulation occurred after SPION and Au-NP treatment, and similar effects were observed after C. elegans exposure to arsenic, cadmium and ethosuximide. (Chen et al, 2013, Chen et al, 2015, Petryszak et al, 2016 Hence, the effects of SPIONs in iron homeostasis might be part of a more general response to toxicants and not necessarily linked to oxidative dissolution of the SPION core into free iron.…”

Section: Evaluation Of Specific Molecular Markersmentioning

confidence: 99%

Toxicogenomics of iron oxide nanoparticles in the nematodeC. elegans

Gonzalez-Moragas

Benseny‐Cases

et al. 2017

Nanotoxicology

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Toxicogenomics of iron oxide nanoparticles in the nematode C. elegansWe present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in C. elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated. The role of oxidative stress was confirmed by gene expression analysis and by synchrotron Fourier Transform infrared microscopy based on the higher tissue oxidation of NP-treated animals. The observed transcriptional modulation of key signaling pathways such as MAPK and Wnt suggests that SPIONs might be endocytosed by clathrin-mediated processes, a putative mechanism of nanotoxicity which deserves further mechanistic investigations.

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Metal-induced neurodegeneration in C. elegans

Cited by 65 publications

References 142 publications

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS

Toxicogenomics of iron oxide nanoparticles in the nematodeC. elegans

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