Toxicity Induction in Neurons and Muscle in Nematodes Exposed to Environmental Toxicants or Stresses

  • Dayong Wang


Neurons and muscle are potential secondary targeted organs for environmental toxicants in nematodes. We here first discussed the toxicity on development and functions of neurons in nematodes exposed to environmental toxicants or stresses. Six aspects of neurotoxicity induced by environmental toxicants or stresses were mainly introduced, and they are development and function of GABAergic neurons, development of dopaminergic neurons, development and function of sensory neurons, interneurons, complex behaviors, and neurotransmission. The toxicity on development and functions of muscle in nematodes exposed to environmental toxicants or stresses was further introduced and discussed.


Damage on neurons Damage on muscle Environmental exposure Caenorhabditis elegans 


  1. 1.
    Wang D-Y (2018) Nanotoxicology in Caenorhabditis elegans. Springer, SingaporeCrossRefGoogle Scholar
  2. 2.
    Wang D-Y (2018) Molecular toxicology in Caenorhabditis elegans. Springer, SingaporeCrossRefGoogle Scholar
  3. 3.
    Yin J-C, Liu R, Jian Z-H, Yang D, Pu Y-P, Yin L-H, Wang D-Y (2018) Di (2-ethylhexyl) phthalate-induced reproductive toxicity involved in DNA damage-dependent oocyte apoptosis and oxidative stress in Caenorhabditis elegans. Ecotoxicol Environ Saf 163:298–306PubMedCrossRefGoogle Scholar
  4. 4.
    Shao H-M, Han Z-Y, Krasteva N, Wang D-Y (2018) Identification of signaling cascade in the insulin signaling pathway in response to nanopolystyrene particles. Nanotoxicology.
  5. 5.
    Ruan Q-L, Qiao Y, Zhao Y-L, Xu Y, Wang M, Duan J-A, Wang D-Y. (2016) Beneficial effects of Glycyrrhizae radix extract in preventing oxidative damage and extending the lifespan of Caenorhabditis elegans. J Ethnopharmacol 177: 101–110PubMedCrossRefGoogle Scholar
  6. 6.
    Xiao G-S, Zhao L, Huang Q, Yang J-N, Du H-H, Guo D-Q, Xia M-X, Li G-M, Chen Z-X, Wang D-Y (2018) Toxicity evaluation of Wanzhou watershed of Yangtze Three Gorges Reservoir in the flood season in Caenorhabditis elegans. Sci Rep 8:6734PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Xiao G-S, Zhao L, Huang Q, Du H-H, Guo D-Q, Xia M-X, Li G-M, Chen Z-X, Wang D-Y (2018) Biosafety assessment of water samples from Wanzhou watershed of Yangtze Three Gorges Reservoir in the quiet season in Caenorhabditis elegans. Sci Rep 8:14102PubMedCrossRefGoogle Scholar
  8. 8.
    Qu M, Xu K-N, Li Y-H, Wong G, Wang D-Y (2018) Using acs-22 mutant Caenorhabditis elegans to detect the toxicity of nanopolystyrene particles. Sci Total Environ 643:119–126PubMedCrossRefGoogle Scholar
  9. 9.
    Dong S-S, Qu M, Rui Q, Wang D-Y (2018) Combinational effect of titanium dioxide nanoparticles and nanopolystyrene particles at environmentally relevant concentrations on nematodes Caenorhabditis elegans. Ecotoxicol Environ Saf 161:444–450PubMedCrossRefGoogle Scholar
  10. 10.
    Wang D-Y, Yu Y-L, Li Y-X, Wang Y, Wang D-Y (2014) Dopamine receptors antagonistically regulate behavioral choice between conflicting alternatives in C. elegans. PLoS ONE 9:e115985PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Yu Y-L, Zhi L-T, Wu Q-L, Jing L-N, Wang D-Y (2018) NPR-9 regulates innate immune response in Caenorhabditis elegans by antagonizing activity of AIB interneurons. Cell Mol Immunol 15:27–37PubMedCrossRefGoogle Scholar
  12. 12.
    Li Y-X, Yu S-H, Wu Q-L, Tang M, Pu Y-P, Wang D-Y (2012) Chronic Al2O3-nanoparticle exposure causes neurotoxic effects on locomotion behaviors by inducing severe ROS production and disruption of ROS defense mechanisms in nematode Caenorhabditis elegans. J Hazard Mater 219–220:221–230PubMedCrossRefGoogle Scholar
  13. 13.
    Du M, Wang D-Y (2009) The neurotoxic effects of heavy metal exposure on GABAergic system in nematode Caenorhabditis elegans. Environ Toxicol Pharmacol 27:314–320PubMedCrossRefGoogle Scholar
  14. 14.
    Li Y-P, Li Y-X, Wu Q-L, Ye H-Y, Sun L-M, Ye B-P, Wang D-Y (2013) High concentration of vitamin E decreases thermosensation and thermotaxis learning and the underlying mechanisms in nematode Caenorhabditis elegans. PLoS One 8:e71180PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Yu X-M, Guan X-M, Wu Q-L, Zhao Y-L, Wang D-Y (2015) Vitamin E ameliorates the neurodegeneration related phenotypes caused by neurotoxicity of Al2O3-nanoparticles in C. elegans. Toxicol Res 4:1269–1281CrossRefGoogle Scholar
  16. 16.
    Ju J-J, Ruan Q-L, Li X-B, Liu R, Li Y-H, Pu Y-P, Yin L-H, Wang D-Y (2013) Neurotoxicological evaluation of microcystin-LR exposure at environmental relevant concentrations on nematode Caenorhabditis elegans. Environ Sci Pollut Res 20:1823–1830CrossRefGoogle Scholar
  17. 17.
    Negga R, Stuart JA, Machen ML, Salva J, Lizek AJ, Richardson SJ, Osborne AS, Mirallas O, McVey KA, Fitsanakis VA (2012) Exposure to glyphosate- and/or Mn/Zn-ethylene-bis-dithiocarbamate-containing pesticides leads to degeneration of γ-aminobutyric acid and dopamine neurons in Caenorhabditis elegans. Neurotox Res 21:281–290PubMedCrossRefGoogle Scholar
  18. 18.
    Zhao Y-L, Wu Q-L, Li Y-P, Wang D-Y (2013) Translocation, transfer, and in vivo safety evaluation of engineered nanomaterials in the non-mammalian alternative toxicity assay model of nematode Caenorhabditis elegans. RSC Adv 3:5741–5757CrossRefGoogle Scholar
  19. 19.
    Ding X-C, Rui Q, Wang D-Y (2018) Functional disruption in epidermal barrier enhances toxicity and accumulation of graphene oxide. Ecotoxicol Environ Saf 163:456–464PubMedCrossRefGoogle Scholar
  20. 20.
    Zhao L, Kong J-T, Krasteva N, Wang D-Y (2018) Deficit in epidermal barrier induces toxicity and translocation of PEG modified graphene oxide in nematodes. Toxicol Res 7:1061–1070CrossRefGoogle Scholar
  21. 21.
    Wang Q-Q, Zhao S-Q, Zhao Y-L, Rui Q, Wang D-Y (2014) Toxicity and translocation of graphene oxide in Arabidopsis plants under stress conditions. RSC Adv 4:60891–60901CrossRefGoogle Scholar
  22. 22.
    Zhao Y-L, Wang X, Wu Q-L, Li Y-P, Tang M, Wang D-Y (2015) Quantum dots exposure alters both development and function of D-type GABAergic motor neurons in nematode Caenorhabditis elegans. Toxicol Res 4:399–408CrossRefGoogle Scholar
  23. 23.
    Wang D-Y, Xing X-J (2008) Assessment of locomotion behavioral defects induced by acute toxicity from heavy metal exposure in nematode Caenorhabditis elegans. J Environ Sci 20:1132–1137CrossRefGoogle Scholar
  24. 24.
    Zhao Y-L, Wang X, Wu Q-L, Li Y-P, Wang D-Y (2015) Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans. J Hazard Mater 283:480–489PubMedCrossRefGoogle Scholar
  25. 25.
    Li J, Li D, Yang Y, Xu T, Li P, He D (2016) Acrylamide induces locomotor defects and degeneration of dopamine neurons in Caenorhabditis elegans. J Appl Toxicol 36:60–67PubMedCrossRefGoogle Scholar
  26. 26.
    McVey KA, Snapp IB, Johnson MB, Negga R, Pressley AS, Fitsanakis VA (2016) Exposure of C. elegans eggs to a glyphosate-containing herbicide leads to abnormal neuronal morphology. Neurotoxicol Teratol 55:23–31PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Mashock MJ, Zanon T, Kappell AD, Petrella LN, Andersen EC, Hristova KR (2016) Copper oxide nanoparticles impact several toxicological endpoints and cause neurodegeneration in Caenorhabditis elegans. PLoS One 11:e0167613PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Zhi L-T, Yu Y-L, Jiang Z-X, Wang D-Y (2017) mir-355 functions as an important link between p38 MAPK signaling and insulin signaling in the regulation of innate immunity. Sci Rep 7:14560PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Sun L-M, Liao K, Hong C-C, Wang D-Y (2017) Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction. PLoS One 12:e0172228PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Sun L-M, Liao K, Wang D-Y (2017) Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans. PLoS One 12:e0184003PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Yu Y-L, Zhi L-T, Guan X-M, Wang D-Y, Wang D-Y (2016) FLP-4 neuropeptide and its receptor in a neuronal circuit regulate preference choice through functions of ASH-2 trithorax complex in Caenorhabditis elegans. Sci Rep 6:21485PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Sun L-M, Liao K, Li Y-P, Zhao L, Liang S, Guo D, Hu J, Wang D-Y (2016) Synergy between PVP-coated silver nanoparticles and azole antifungal against drug-resistant Candida albicans. J Nanosci Nanotechnol 16:2325–2335PubMedCrossRefGoogle Scholar
  33. 33.
    Caldwell KA, Tucci ML, Armagost J, Hodges TW, Chen J, Memon SB, Blalock JE, DeLeon SM, Findlay RH, Ruan Q, Webber PJ, Standaert DG, Olson JB, Caldwell GA (2009) Investigating bacterial sources of toxicity as an environmental contributor to dopaminergic neurodegeneration. PLoS One 4(10):e7227PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Sammi SR, Agim ZS, Cannon JR (2018) Harmane-induced selective dopaminergic neurotoxicity in Caenorhabditis elegans. Toxicol Sci 161:335–348PubMedCrossRefGoogle Scholar
  35. 35.
    Reckziegel P, Chen P, Caito S, Gubert P, Soares FAA, Fachinetto R, Aschner M (2016) Extracellular dopamine and alterations on dopamine transporter are related to reserpine toxicity in Caenorhabditis elegans. Arch Toxicol 90:633–645PubMedCrossRefGoogle Scholar
  36. 36.
    VanDuyn N, Settivari R, Wong G, Nass R (2010) SKN-1/Nrf2 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of methylmercury toxicity. Toxicol Sci 118:613–624PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Benedetto A, Au C, Avila DS, Milatovic D, Aschner M (2010) Extracellular dopamine potentiates Mn-induced oxidative stress, lifespan reduction, and dopaminergic neurodegeneration in a BLI-3–dependent manner in Caenorhabditis elegans. PLoS Genet 6:e1001084PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Chakraborty S, Michael Aschner M (2012) Altered manganese homeostasis: implications for BLI-3-dependent dopaminergic neurodegeneration and SKN-1 protection in C. elegans. J Trace Elem Med Biol 26:183–187PubMedCrossRefGoogle Scholar
  39. 39.
    VanDuyn N, Settivari R, LeVora J, Zhou S, Unrine J, Nass R (2013) The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration. J Neurochem 124:147–157PubMedCrossRefGoogle Scholar
  40. 40.
    VanDuyn N, Nass R (2014) The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans. J Neurochem 128:962–974PubMedCrossRefGoogle Scholar
  41. 41.
    Ijomone OM, Miah MR, Peres TV, Nwoha PU, Aschner M (2016) Null allele mutants of trt-1, the catalytic subunit of telomerase in Caenorhabditis elegans, are less sensitive to Mn-induced toxicity and DAergic degeneration. Neutotoxicology 57:54–60CrossRefGoogle Scholar
  42. 42.
    Xing X-J, Du M, Zhang Y-F, Wang D-Y (2009) Adverse effects of metal exposure on chemotaxis towards water-soluble attractants regulated mainly by ASE sensory neuron in nematode Caenorhabditis elegans. J Environ Sci 21:1684–1694CrossRefGoogle Scholar
  43. 43.
    Li Y-H, Ye H-Y, Du M, Zhang Y-F, Ye B-P, Pu Y-P, Wang D-Y (2009) Induction of chemotaxis to sodium chloride and diacetyl and thermotaxis defects by microcystin-LR exposure in nematode Caenorhabditis elegans. J Environ Sci 21:971–979CrossRefGoogle Scholar
  44. 44.
    Chen N, Li J, Li D, Yang Y, He D (2014) Chronic exposure to perfluorooctane sulfonate induces behavior defects and neurotoxicity through oxidative damages, in vivo and in vitro. PLoS One 9:e113453PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Wu Q-L, Cao X-O, Yan D, Wang D-Y, Aballay A (2015) Genetic screen reveals link between maternal-effect sterile gene mes-1 and P. aeruginosa-induced neurodegeneration in C. elegans. J Biol Chem 290:29231–29239PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Bargmann CI, Horvitz HR (1991) Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron 7:729–742PubMedCrossRefGoogle Scholar
  47. 47.
    Uchida O, Nakano H, Koga M, Ohshima Y (2003) The C. elegans che-1 gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons. Development 130:1215–1224PubMedCrossRefGoogle Scholar
  48. 48.
    Xing X-J, Du M, Xu X-M, Rui Q, Wang D-Y (2009) Exposure to metals induces morphological and functional alteration of AFD neurons in nematode Caenorhabditis elegans. Environ Toxicol Pharmacol 28:104–110PubMedCrossRefGoogle Scholar
  49. 49.
    Wu Q-L, Liu P-D, Li Y-X, Du M, Xing X-J, Wang D-Y (2012) Inhibition of ROS elevation and damage on mitochondrial function prevents lead-induced neurotoxic effects on structures and functions of AFD neurons in Caenorhabditis elegans. J Environ Sci 24:733–742CrossRefGoogle Scholar
  50. 50.
    Tseng I-L, Yang Y-F, Yu C-W, Li W-H, VH-C L (2013) Phthalates induce neurotoxicity affecting locomotor and thermotactic behaviors and AFD neurons through oxidative stress in Caenorhabditis elegans. PLoS One 8:e82657PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Yu C-W, Liao VH-C (2014) Arsenite induces neurotoxic effects on AFD neurons via oxidative stress in Caenorhabditis elegans. Metallomics 6:1824–1831PubMedCrossRefGoogle Scholar
  52. 52.
    Swoboda P, Adler HT, Thomas JH (2000) The RFX-type transcription factor DAF-19 regulates sensory neuron cilium formation in C. elegans. Mol Cell 5:411–421PubMedCrossRefGoogle Scholar
  53. 53.
    Satterlee JS, Sasakura H, Kuhara A, Berkeley M, Mori I, Sengupta P (2001) Specification of thermosensory neuron fate in C. elegans requires ttx-1, a homolog of otd/Otx. Neuron 31:943–956PubMedCrossRefGoogle Scholar
  54. 54.
    Gourgou E, Chronis N (2016) Chemically induced oxidative stress affects ASH neuronal function and behavior in C. elegans. Sci Rep 6:38147PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Meisel JD, Kim DH (2016) Inhibition of lithium-sensitive phosphatase BPNT-1 causes selective neuronal dysfunction in C. elegans. Curr Biol 26:1922–1928PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Moore CE, Lein PJ, Puschner B (2014) Microcystins alter chemotactic behavior in Caenorhabditis elegans by selectively targeting the AWA sensory neuron. Toxins 6:1813–1836PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Sengupta P, Chou JH, Bargmann CI (1996) odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell 84:899–909PubMedCrossRefGoogle Scholar
  58. 58.
    Colosimo ME, Tran S, Sengupta P (2003) The divergent orphan nuclear receptor odr-7 regulates olfactory neuron gene expression via multiple mechanisms in Caenorhabditis elegans. Genetics 165:1779–1791PubMedPubMedCentralGoogle Scholar
  59. 59.
    Donohoe DR, Weeks K, Aamodt EJ, Dwyer DS (2008) Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in C. elegans. Int J Dev Neurosci 26:371–380PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Hobert O, Mori I, Yamashita Y, Honda H, Ohshima Y, Liu Y, Ruvkun G (1997) Regulation of interneuron function in the C. elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene. Neuron 19:345–357PubMedCrossRefGoogle Scholar
  61. 61.
    Pocock R, Hobert O (2008) Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Nat Neurosci 11:894–900PubMedCrossRefGoogle Scholar
  62. 62.
    Ye H-Y, Ye B-P, Wang D-Y (2006) Learning and learning choice in the nematode Caenorhabditis elegans. Neurosci Bull 22:355–360PubMedGoogle Scholar
  63. 63.
    Zhang Y-F, Ye B-P, Wang D-Y (2010) Effects of metal exposure on associative learning behavior in nematode Caenorhabditis elegans. Arch Environ Contam Toxicol 59:129–136PubMedCrossRefGoogle Scholar
  64. 64.
    Ye H-Y, Ye B-P, Wang D-Y (2008) Molecular control of memory in nematode Caenorhabditis elegans. Neurosci Bull 24:49–55PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Ye H-Y, Ye B-P, Wang D-Y (2008) Evaluation of the long-term memory for the thermosensation regulation by NCS-1 in Caenorhabditis elegans. Neurosci Bull 24:1–6PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Wang W-H, Cheng L-C, Pan F-Y, Xue B, Wang D-Y, Chen Z, Li C-J (2011) Intracellular trafficking of histone deacetylase 4 regulates long-term memory formation. Anat Rec 294:1025–1034CrossRefGoogle Scholar
  67. 67.
    Li Y-X, Zhao Y-L, Huang X, Li X-F, Guo Y-L, Wang D-Y, Li C-J, Wang D-Y (2013) Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans. PLoS One 8:e77779PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Ye H-Y, Ye B-P, Wang D-Y (2008) Trace administration of vitamin E can retrieve and prevent UV-irradiation- and metal exposure-induced memory deficits in nematode Caenorhabditis elegans. Neurobiol Learn Mem 90:10–18PubMedCrossRefGoogle Scholar
  69. 69.
    Li Y-X, Wang Y, Hu Y-O, Zhong J-X, Wang D-Y (2011) Modulation of the assay system for the sensory integration of 2 sensory stimuli that inhibit each other in nematode Caenorhabditis elegans. Neurosci Bull 27:69–82PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Xing X-J, Rui Q, Du M, Wang D-Y (2009) Exposure to lead and mercury in young larvae induces more severe deficits in neuronal survival and synaptic function than in adult nematodes. Arch Environ Contam Toxicol 56:732–741PubMedCrossRefGoogle Scholar
  71. 71.
    Wang D-Y, Wang Y (2009) HLB-1 functions as a new regulator for the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans. Neurosci Bull 25:75–86PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD (2003) Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc Natl Acad Sci U S A 100:9980–9985PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Momma K, Homma T, Isaka R, Sudevan S, Higashitani A (2017) Heat-induced calcium leakage causes mitochondrial damage in Caenorhabditis elegans body-wall muscles. Genetics 206:1985–1994PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Lee AL, Ung HM, Sands LP, Kikis EA (2017) A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles. PLoS One 12:e0173644PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Shen L-L, Wang D-Y (2005) Differentiation and function of presynaptic active zone. Neurosci Bull 21:335–343Google Scholar
  76. 76.
    Sun Y, Zhao Y-N, Wang D-Y (2006) Computational analysis of genetic loci required for synapse structure and function and their corresponding microRNAs in C. elegans. Neurosci Bull 22:339–349PubMedGoogle Scholar
  77. 77.
    Wang D-Y, Wang Y (2006) Screening for genetic loci affecting the active zone formation in C. elegans. Neurosci Bull 22:301–304PubMedGoogle Scholar
  78. 78.
    Chen H, Li H-R, Wang D-Y (2017) Graphene oxide dysregulates Neuroligin/NLG-1-mediated molecular signaling in interneurons in Caenorhabditis elegans. Sci Rep 7:41655PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Dayong Wang
    • 1
  1. 1.School of MedicineSoutheast UniversityNanjingChina

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