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Abnormal development of motor neurons in perfluorooctane sulphonate exposed zebrafish embryos

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Abstract

Perfluorooctane sulfonate (PFOS) is an environmental organic pollutant, the potential neurotoxicity of which is causing great concern in fish. In the present study, we examined the effects of PFOS on motor neurons, and investigated the potential toxicological mechanisms oxidative stress in zebrafish embryos. Six-hour post-fertilization (hpf) zebrafish embryos were exposed to 1.0 mg/L PFOS, then we examined the expression of alpha-tubulin, proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 5 (CDK5), and peroxiredoxin 2 (PRX2) after PFOS exposure until 120 hpf. The results showed that PFOS increased alpha-tubulin in the coccygeal spinal cord (CSC) at 96 hpf, whereas decreased alpha-tubulin in the brain and spinal cord at 120 hpf. PCNA expression was highly increased in CSC and abdomen compared with control at 96 and 120 hpf after PFOS exposure. In addition, PFOS exposure caused CDK5 expression to be highly increased in brain region following by down-regulation of PRX2 expression at 96 hpf. These results indicated that, at least in part, the effect on motor neurons induced by PFOS was mediated by dynamically interfering with the expression of alpha-tubulin and PCNA. Furthermore, PFOS-induced toxicity was associated with oxidative stress by deregulating CDK5 and PRX2.

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Abbreviations

PFOS:

Perfluorooctane sulfonate

PFCs:

Perfluorooctanesulfonyl fluoride

PCNA:

Proliferating cell nuclear antigen

CDK5:

Cyclin-dependent kinase 5

PRX2:

Peroxiredoxin 2

CSC:

Coccygeal spinal cord

DMSO:

Dimethyl sulfoxide

IHC:

Immunohistochemistry

QPCR:

Quantitative real-time PCR

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

LSD:

Least significant difference

PE:

Pericardium edema

CS:

Curved spines

ED:

Embryonic dissolution

BN:

Brain necrosis

References

  • Asakawa A, Toyoshima M, Fujimiya M, Harada K, Ataka K, Inoue K, Koizumi A (2007) Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus. Int J Mol Med 19(5):733–739

    CAS  Google Scholar 

  • Baker K, Warren KS, Yellen G, Fishman MC (1997) Defective “pacemaker” current (Ih) in a zebrafish mutant with a slow heart rate. Proc Natl Acad Sci USA 94(9):4554–4559

    Article  CAS  Google Scholar 

  • Biesiada E, Adams PM, Shanklin DR, Bloom GS, Stein SA (1996) Biology of the congenitally hypothyroid hyt/hyt mouse. Adv Neuroimmunol 6(4):309–346

    Article  CAS  Google Scholar 

  • Dhavan R, Tsai LH (2001) A decade of CDK5. Nat Rev Mol Cell Biol 2(10):749–759

    Article  CAS  Google Scholar 

  • Giesy JP, Kannan K (2002) Perfluorochemical surfactants in the environment. Environ Sci Technol 36(7):146A–152A

    Article  CAS  Google Scholar 

  • Goldman D, Hankin M, Li Z, Dai X, Ding J (2001) Transgenic zebrafish for studying nervous system development and regeneration. Transgenic Res 10(1):21–33

    Article  CAS  Google Scholar 

  • Grasty RC, Wolf DC, Grey BE, Lau CS, Rogers JM (2003) Prenatal window of susceptibility to perfluorooctane sulfonate-induced neonatal mortality in the Sprague-Dawley rat. Birth Defects Res B Dev Reprod Toxicol 68(6):465–471

    Article  CAS  Google Scholar 

  • Grasty RC, Bjork JA, Wallace KB, Wolf DC, Lau CS, Rogers JM (2005) Effects of prenatal perfluorooctane sulfonate (PFOS) exposure on lung maturation in the perinatal rat. Birth Defects Res B Dev Reprod Toxicol 74(5):405–416

    Article  CAS  Google Scholar 

  • Hu W, Cheng L, Xia H, Sun D, Li D, Li P, Song Y, Ma X (2009) Teratogenic effects of sodium thiosulfate on developing zebrafish embryos. Front Biosci 14:3680–3687

    Article  CAS  Google Scholar 

  • Huang H, Huang C, Wang L, Ye X, Bai C, Simonich MT, Tanguay RL, Dong Q (2010) Toxicity, uptake kinetics and behavior assessment in zebrafish embryos following exposure to perfluorooctanesulphonicacid (PFOS). Aquat Toxicol 98(2):139–147

    Article  CAS  Google Scholar 

  • Jin MH, Lee YH, Kim JM, Sun HN, Moon EY, Shong MH, Kim SU, Lee SH, Lee TH, Yu DY, Lee DS (2005) Characterization of neural cell types expressing peroxiredoxins in mouse brain. Neurosci Lett 381(3):252–257

    Article  CAS  Google Scholar 

  • Johansson N, Fredriksson A, Eriksson P (2008) Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology 29(1):160–169

    Article  CAS  Google Scholar 

  • Johansson N, Eriksson P, Viberg H (2009) Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain. Toxicol Sci 108(2):412–418

    Article  CAS  Google Scholar 

  • Kanungo J, Li BS, Zheng Y, Pant HC (2006) Cyclin-dependent kinase 5 influences Rohon-Beard neuron survival in zebrafish. J Neurochem 99(1):251–259

    Article  CAS  Google Scholar 

  • Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203(3):253–310

    Article  CAS  Google Scholar 

  • Lau C, Butenhoff JL, Rogers JM (2004) The developmental toxicity of perfluoroalkyl acids and their derivatives. Toxicol Appl Pharmacol 198(2):231–241

    Article  CAS  Google Scholar 

  • Lau C, Anitole K, Hodes C, Lai D, Pfahles-Hutchens A, Seed J (2007) Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 99(2):366–394

    Article  CAS  Google Scholar 

  • Lee JH, Kim HS, Lee SJ, Kim KT (2007) Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death. J Cell Sci 120(Pt 13):2259–2271

    Article  CAS  Google Scholar 

  • Li BS, Sun MK, Zhang L, Takahashi S, Ma W, Vinade L, Kulkarni AB, Brady RO, Pant HC (2001) Regulation of NMDA receptors by cyclin-dependent kinase-5. Proc Natl Acad Sci USA 98(22):12742–12747

    Article  CAS  Google Scholar 

  • Liu X, Liu W, Jin Y, Yu W, Liu L, Yu H (2010a) Effects of subchronic perfluorooctane sulfonate exposure of rats on calcium-dependent signaling molecules in the brain tissue. Arch Toxicol 84(6):471–479

    Article  CAS  Google Scholar 

  • Liu Y, Wang J, Fang X, Zhang H, Dai J (2010b) The thyroid-disrupting effects of long-term perfluorononanoate exposure on zebrafish (Danio rerio). Ecotoxicology. doi:10.1007/s10646-010-0555-3

  • Luebker DJ, York RG, Hansen KJ, Moore JA, Butenhoff JL (2005) Neonatal mortality from in utero exposure to perfluorooctanesulfonate (PFOS) in Sprague-Dawley rats: dose-response, and biochemical and pharamacokinetic parameters. Toxicology 215(1–2):149–169

    Article  CAS  Google Scholar 

  • Naryzhny SN (2008) Proliferating cell nuclear antigen: a proteomics view. Cell Mol Life Sci 65(23):3789–3808

    Article  CAS  Google Scholar 

  • Qu D, Rashidian J, Mount MP, Aleyasin H, Parsanejad M, Lira A, Haque E, Zhang Y, Callaghan S, Daigle M, Rousseaux MW, Slack RS, Albert PR, Vincent I, Woulfe JM, Park DS (2007) Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson’s disease. Neuron 55(1):37–52

    Article  CAS  Google Scholar 

  • Renner R (2001) Growing concern over perfluorinated chemicals. Environ Sci Technol 35(7):154A–160A

    Article  CAS  Google Scholar 

  • Rivera-Perez JA, Mager J, Magnuson T (2003) Dynamic morphogenetic events characterize the mouse visceral endoderm. Dev Biol 261(2):470–487

    Article  CAS  Google Scholar 

  • Senthilkumar K, Ohi E, Sajwan K, Takasuga T, Kannan K (2007) Perfluorinated compounds in river water, river sediment, market fish, and wildlife samples from Japan. Bull Environ Contam Toxicol 79(4):427–431

    Article  CAS  Google Scholar 

  • Shelton SB, Johnson GV (2004) Cyclin-dependent kinase-5 in neurodegeneration. J Neurochem 88(6):1313–1326

    Article  CAS  Google Scholar 

  • Shi X, Zhou B (2010) The role of Nrf2 and MAPK pathways in PFOS-induced oxidative stress in zebrafish embryos. Toxicol Sci 115(2):391–400

    Article  CAS  Google Scholar 

  • Shi X, Du Y, Lam PK, Wu RS, Zhou B (2008) Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS. Toxicol Appl Pharmacol 230(1):23–32

    Article  CAS  Google Scholar 

  • Shi X, Yeung LW, Lam PK, Wu RS, Zhou B (2009) Protein profiles in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonate. Toxicol Sci 110(2):334–340

    Article  CAS  Google Scholar 

  • Sinclair E, Mayack DT, Roblee K, Yamashita N, Kannan K (2006) Occurrence of perfluoroalkyl surfactants in water, fish, and birds from New York State. Arch Environ Contam Toxicol 50(3):398–410

    Article  CAS  Google Scholar 

  • Slevin M, Krupinski J (2009) Cyclin-dependent kinase-5 targeting for ischaemic stroke. Curr Opin Pharmacol 9(2):119–124

    Article  CAS  Google Scholar 

  • Slotkin TA, MacKillop EA, Melnick RL, Thayer KA, Seidler FJ (2008) Developmental neurotoxicity of perfluorinated chemicals modeled in vitro. Environ Health Perspect 116(6):716–722

    Article  CAS  Google Scholar 

  • Sun KH, de Pablo Y, Vincent F, Shah K (2008) Deregulated Cdk5 promotes oxidative stress and mitochondrial dysfunction. J Neurochem 107(1):265–278

    Article  CAS  Google Scholar 

  • Ton C, Lin Y, Willett C (2006) Zebrafish as a model for developmental neurotoxicity testing. Birth Defects Res A Clin Mol Teratol 76(7):553–567

    Article  CAS  Google Scholar 

  • van der Meulen T, Schipper H, van den Boogaart JG, Huising MO, Kranenbarg S, van Leeuwen JL (2006) Endurance exercise differentially stimulates heart and axial muscle development in zebrafish (Danio rerio). Am J Physiol Regul Integr Comp Physiol 291(4):R1040–R1048

    Article  Google Scholar 

  • Wang CX, Song JH, Song DK, Yong VW, Shuaib A, Hao C (2006) Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2. Cell Death Differ 13(7):1203–1212

    Article  CAS  Google Scholar 

  • Wilhelm M, Holzer J, Dobler L, Rauchfuss K, Midasch O, Kraft M, Angerer J, Wiesmuller G (2009) Preliminary observations on perfluorinated compounds in plasma samples (1977–2004) of young German adults from an area with perfluorooctanoate-contaminated drinking water. Int J Hyg Environ Health 212(2):142–145

    Article  CAS  Google Scholar 

  • Wilson SW, Brand M, Eisen JS (2002) Patterning the zebrafish central nervous system. Results Probl Cell Differ 40:181–215

    CAS  Google Scholar 

  • Zeng HC, Li YY, Zhang L, Wang YJ, Chen J, Xia W, Lin Y, Wei J, Lv ZQ, Li M, Xu SQ (2010a) Prenatal exposure to perfluorooctanesulfonate in rat resulted in long-lasting changes of expression of synapsins and synaptophysin. Synapse

  • Zeng HC, Zhang L, Li YY, Wang YJ, Xia W, Lin Y, Wei J, Xu SQ (2010b) Inflammation-like glial response in rat brain induced by prenatal PFOS exposure. Neurotoxicology. doi:10.1016/j.neuro.2010.10.001

  • Zhang L, Li YY, Zeng HC, Wei J, Wan YJ, Chen J, Xu SQ (2010) MicroRNA expression changes during zebrafish development induced by perfluorooctane sulfonate. J Appl Toxicol

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (81030051, 20807017), the R&D Special Fund for Public Welfare Industry (Environment) (200909102), the National High Technology Research and Program of China (2008AA062504), and the Fundamental Research Funds for Huazhong University of Science & Technology (HUST) (2010MS091).

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Authors and Affiliations

  1. Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ling Zhang, Yuan-yuan Li, Tian Chen, Wei Xia, Yin Zhou, Yan-jian Wan, Zi-quan Lv, Geng-qi Li & Shun-qing Xu

  2. Department of Preventive Medicine, Medical College, Wuhan University of Science and Technology, Wuhan, 430065, China

    Ling Zhang

  3. Microbiology & Biochemical Pharmacy, Wuhan Polytechnic University, Wuhan, 430023, China

    Yin Zhou

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  1. Ling Zhang
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  2. Yuan-yuan Li
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Correspondence to Shun-qing Xu.

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Ling Zhang, Yuan-yuan Li, Both authors contributed equally to this work.

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Zhang, L., Li, Yy., Chen, T. et al. Abnormal development of motor neurons in perfluorooctane sulphonate exposed zebrafish embryos. Ecotoxicology 20, 643–652 (2011). https://doi.org/10.1007/s10646-011-0604-6

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