Neuronal Signaling Pathways Required for the Regulation of Toxicity of Environmental Toxicants or Stresses

  • Dayong Wang


In this chapter, we focused on the introduction of important roles of neuronal signaling pathways in regulating the toxicity of environmental toxicants or stresses in nematodes. We first introduced and discussed the functions of neuronal MAPK signaling pathways (JNK and ERK MAPKs), TGF-β signaling pathway (both DAF-7- and DBL-1-mediated TGF-β signaling pathways), G-protein-coupled receptors (GPCRs) and G proteins, and neuropeptide proteins in the regulation of toxicity of environmental toxicants or stresses. Moreover, the effects of neuronal signals (INS-7, XBP-1, dopamine and serotonin signals, and Wnt signaling) on functions of molecular signals in other tissues or organs (especially the intestine) in the regulation of toxicity of environmental toxicants or stresses were further introduced and discussed.


Neuronal signaling pathway 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.
    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 8:14102CrossRefGoogle Scholar
  4. 4.
    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:e115985CrossRefGoogle Scholar
  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: 101–110CrossRefGoogle Scholar
  6. 6.
    Koga M, Zwaal R, Guan KL, Avery L, Ohshima Y (2000) A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress responses. EMBO J 19:5148–5156CrossRefGoogle Scholar
  7. 7.
    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
  8. 8.
    Zhao 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.
  9. 9.
    Zhao Y-L, Wu Q-L, Wang D-Y (2015) A microRNAs-mRNAs network involved in the control of graphene oxide toxicity in Caenorhabditis elegans. RSC Adv 5:92394–92405CrossRefGoogle Scholar
  10. 10.
    Okuyama T, Inoue H, Ookuma S, Satoh T, Kano K, Honjoh S, Hisamoto N, Matsumoto K, Nishida E (2010) The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans. J Biol Chem 285:30274–30281CrossRefGoogle Scholar
  11. 11.
    Qu M, Li Y-H, Wu Q-L, Xia Y-K, Wang D-Y (2017) Neuronal ERK signaling in response to graphene oxide in nematode Caenorhabditis elegans. Nanotoxicology 11:520–533CrossRefGoogle Scholar
  12. 12.
    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 7:41655CrossRefGoogle Scholar
  13. 13.
    Kim H, Jeong J, Chatterjee N, Roca CP, Yoon D, Kim S, Kim Y, Choi J (2017) JAK/STAT and TGF-β activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans. Sci Rep 7:17833CrossRefGoogle Scholar
  14. 14.
    Ren M-X, Zhao L, Lv X, Wang D-Y (2017) Antimicrobial proteins in the response to graphene oxide in Caenorhabditis elegans. Nanotoxicology 11:578–590CrossRefGoogle Scholar
  15. 15.
    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:e0184003CrossRefGoogle Scholar
  16. 16.
    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 16:2325–2335CrossRefGoogle Scholar
  17. 17.
    Zugasti O, Ewbank JJ (2009) Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-β signaling pathway in Caenorhabditis elegans epidermis. Nat Immunol 10:249–256CrossRefGoogle Scholar
  18. 18.
    Styer KL, Singh V, Macosko E, Steele SE, Bargmann CI, Aballay A (2008) Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science 322:460–464CrossRefGoogle Scholar
  19. 19.
    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 15:27–37CrossRefGoogle Scholar
  20. 20.
    Sun J, Singh V, Kajino-Sakamoto R, Aballay A (2011) Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332:729–732CrossRefGoogle Scholar
  21. 21.
    Sun J, Liu Y, Aballay A (2012) Organismal regulation of XBP-1-mediated unfolded protein response during development and immune activation. EMBO Rep 13:855–860CrossRefGoogle Scholar
  22. 22.
    Maman M, Marques FC, Volovik Y, Dubnikov T, Bejerano-Sagie M, Cohen E (2013) A neuronal GPCR is critical for the induction of the heat shock response in the nematode C. elegans. J Neurosci 33:6102–6111CrossRefGoogle Scholar
  23. 23.
    Los FCO, Ha C, Aroian RV (2013) Neuronal Goα and CAPS regulate behavioral and immune responses to bacterial pore-forming toxins. PLoS ONE 8:e54528CrossRefGoogle Scholar
  24. 24.
    Anderson A, Laurenson-Schafer H, Partridge FA, Hodgkin J, McMullan R (2013) Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells. PLoS Pathog 9:e1003787CrossRefGoogle Scholar
  25. 25.
    Singh V, Aballay A (2012) Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1. J Biol Chem 287:33191–33197CrossRefGoogle Scholar
  26. 26.
    Nath RD, Chow ES, Wang H, Schwarz EM, Sternberg PW (2016) C. elegans stress-induced sleep emerges from the collective action of multiple neuropeptides. Curr Biol 26:2446–2455CrossRefGoogle Scholar
  27. 27.
    Kawil T, Tan M (2008) Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nat Immunol 9:1415–1424CrossRefGoogle Scholar
  28. 28.
    Cao X, Aballay A (2016) Neural inhibition of dopaminergic signaling enhances immunity in a cell non-autonomous manner. Curr Biol 26:2329–2334CrossRefGoogle Scholar
  29. 29.
    Taylor RC, Dillin A (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153:1435–1447CrossRefGoogle Scholar
  30. 30.
    Berendzen KM, Durieux J, Shao L, Tian Y, Kim H, Wolff S, Liu Y, Dillin A (2016) Neuroendocrine coordination of mitochondrial stress signaling and proteostasis. Cell 166:1553–1563CrossRefGoogle Scholar
  31. 31.
    Zhang Q, Wu X, Chen P, Liu L, Xin N, Tian Y, Dillin A (2018) The mitochondrial unfolded protein response is mediated cell-non-autonomously by retromer-dependent Wnt signaling. Cell 174:870–883CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

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

Personalised recommendations