Skip to main content

Advertisement

SpringerLink
Log in

Toxicogenomic Studies of Human Neural Cells Following Exposure to Organophosphorus Chemical Warfare Nerve Agent VX

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Organophosphorus (OP) compounds represent an important group of chemical warfare nerve agents that remains a significant and constant military and civilian threat. OP compounds are considered acting primarily via cholinergic pathways by binding irreversibly to acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Many studies over the past years have suggested that other mechanisms of OP toxicity exist, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. Here we performed a microarray study in which cultured human neural cells were exposed to 0.1 or 10 μM of VX for 1 h. Global gene expression changes were analyzed 6, 24, and 72 h post exposure. Functional annotation and pathway analysis of the differentially expressed genes has revealed many genes, networks and canonical pathways that are related to nervous system development and function, or to neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In particular, the neuregulin pathway impacted by VX exposure has important implications in many nervous system diseases including schizophrenia. These results provide useful information valuable in developing suitable antidotes for more effective prevention and treatment of, as well as in developing biomarkers for, VX-induced chronic neurotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Balali-Mood M, Balali-Mood K (2005) Nerve agents. In: Brent J (ed) Critical care toxicology. Elsevier Mosby, Philadelphia, pp 1379–1393

    Google Scholar 

  2. Black R, Harrison J (1996) The chemistry of organophosphorous chemical warfare agents. In: Hartley FR (ed) The chemistry of organophosphorus compounds. Wiley, Chichester, pp 781–840

    Chapter  Google Scholar 

  3. Morita H, Yanagisawa N, Nakajima T, Shimizu M, Hirabayashi H, Okudera H, Nohara M, Midorikawa Y, Mimura S (1995) Sarin poisoning in Matsumoto, Japan. Lancet 346:290–293

    Article  PubMed  CAS  Google Scholar 

  4. Okumura T, Takasu N, Ishimatsu S, Miyanoki S, Mitsuhashi K, Kumada K, Tanaka K, Hinohara S (1995) Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med 28:129–135

    Article  Google Scholar 

  5. Kwong K (2002) Organophosphate pesticides: biochemistry and clinical toxicology. Ther Drug Monit 24:144–149

    Article  PubMed  CAS  Google Scholar 

  6. McDonough JH Jr, Shih TM (1997) Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev 21:559–579

    Article  PubMed  CAS  Google Scholar 

  7. Wiener SW, Hoffman RS (2004) Nerve agents: a comprehensive review. J Intensive Care Med 19:22–37

    Article  PubMed  Google Scholar 

  8. Eyer P (2003) The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev 22:165–190

    Article  PubMed  CAS  Google Scholar 

  9. Gray AP (1984) Design and structure-activity relationships of antidotes to organophosphorus anticholinesterase agents. Drug Metab Rev 15:557–589

    Article  PubMed  CAS  Google Scholar 

  10. Ray DE (1998) Chronic effects of low level exposure to anticholinesterases—a mechanistic review. Toxicol Lett 102(103):527–533

    Article  PubMed  Google Scholar 

  11. Abou-Donia MB (1981) Organophosphorus ester-induced delayed neurotoxicity. Annu Rev Pharmacol Toxicol 21:511–548

    Article  PubMed  CAS  Google Scholar 

  12. Abou-Donia MB (2003) Organophosphosphorus ester-induced chronic neurotoxicity. Arch Environ Health 58:484–487

    Article  PubMed  CAS  Google Scholar 

  13. Bajgar J (1993) Noncholinergic effects of organophosphates. Ca. Lek Cesk 132:513–517

    CAS  Google Scholar 

  14. Clement JG (1985) Hormonal consequences of organophosphate poisoning. Fundam Appl Toxicol 5:S61–S77

    Article  PubMed  CAS  Google Scholar 

  15. Fautz R, Miltenburger HG (1994) Influence of organophosphorus compounds on different cellular immune functions in vitro. Toxicol In Vitro 8:1027–1031

    Article  PubMed  CAS  Google Scholar 

  16. Tevaljevic L, Bogojevic D, Poznanovic G, Matic S (1990) Toxic response to paraoxon is accompanied by an increased rate of acute phase protein synthesis. Pest Biochem Physiol 38:216–222

    Article  Google Scholar 

  17. Tevaljevic L, Poznanovic G, Ivanovic-Matic S (1992) The acute phase response of rats to soman intoxication. Toxicology 75:1–12

    Article  Google Scholar 

  18. Thrasher JD, Heuser G, Broughton A (2002) Immunological abnormalities in humans chronically exposed to chlorpyrifos. Arch Environ Health 57:181–187

    Article  PubMed  CAS  Google Scholar 

  19. Thrasher JD, Madison R, Broughton A (1993) Immunologic abnormalities in humans exposed to chlorpyrifos: preliminary observations. Arch Environ Health 48:89–93

    Article  PubMed  CAS  Google Scholar 

  20. Newmark J (2004) Therapy for nerve agent poisoning. Arch Neurol 61:649–652

    Article  PubMed  Google Scholar 

  21. Federation of American Scientists (2012) Types of chemical weapons. Fas Org 2012. http://www.fas.org/cw/cwagents.htm. Accessed 03 Jan 2012

  22. Costa LG (2006) Current issues in organophosphate toxicology. Clin Chim Acta 366:1–13

    Article  PubMed  CAS  Google Scholar 

  23. Gwinn MR, Weston A (2008) Application of oligonucleotide microarray technology to toxic occupational exposures. J Toxicol Environ Health A 71:315–324

    Article  PubMed  CAS  Google Scholar 

  24. Mense SM, Sengupta A, Lan C, Zhou M, Bentsman G, Volsky DJ, Whyatt RM, Perera FP, Zhang L (2006) The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes. Toxicol Sci 93:125–135

    Article  PubMed  CAS  Google Scholar 

  25. Moreira EG, Yu X, Robinson JF, Griffith W, Hong SW, Beyer RP, Bammler TK, Faustman EM (2010) Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos. Toxicol Appl Pharmacol 245:310–325

    Article  PubMed  CAS  Google Scholar 

  26. Slotkin T, Seidler F (2009) Transcriptional profiles reveal similarities and differences in the effects of developmental neurotoxicants on differentiation into neurotransmitter phenotypes in PC12 cells. Brain Res Bull 78:211–225

    Article  PubMed  CAS  Google Scholar 

  27. Slotkin TA, Seidler FJ (2007) Comparative developmental neurotoxicity of organophosphates in vivo: transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems. Brain Res Bull 72:232–374

    Article  PubMed  CAS  Google Scholar 

  28. Slotkin TA, Seidler FJ (2009) Protein kinase C is a target for diverse developmental neurotoxicants: transcriptional responses to chlorpyrifos, diazinon, dieldrin and divalent nickel in PC12 cells. Brain Res 1263:23–32

    Article  PubMed  CAS  Google Scholar 

  29. Damodaran TV, Greenfield ST, Patel AG, Dressman HK, Lin SK, Abou-Donia MB (2006) Toxicogenomic studies of the rat brain at an early time point following acute sarin exposure. Neurochem Res 31:367–381

    Article  PubMed  CAS  Google Scholar 

  30. Dillman JF 3rd, Phillips CS, Kniffin DM, Tompkins CP, Hamilton TA, Kan RK (2009) Gene expression profiling of rat hippocampus following exposure to the acetylcholinesterase inhibitor soman. Chem Res Toxicol 22:633–638

    Article  PubMed  CAS  Google Scholar 

  31. Pachiappan A, Thwin MM, Weng Keong L, Lee FK, Manikandan J, Sivakumar V, Gopalakrishnakone P (2009) ETS2 regulating neurodegenerative signaling pathway of human neuronal (SH-SY5Y) cells exposed to single and repeated low-dose sarin (GB). Chem Res Toxicol 22:990–996

    Article  PubMed  CAS  Google Scholar 

  32. Blanton JL, D’Ambrozio JA, Sistrunk JE, Midboe EG (2004) Global changes in the expression patterns of RNA isolated from the hippocampus and cortex of VX exposed mice. J Biochem Mol Toxicol 18:115–123

    Article  PubMed  CAS  Google Scholar 

  33. Wang Y, Weiss MT, Yin J, Tenn CC, Nelson PD, Mikler JR (2008) Protective effects of N-methyl-D-aspartate receptor antagonism on VX-induced neuronal cell death in cultured rat cortical neurons. Neurotox Res 13:163–172

    Article  PubMed  CAS  Google Scholar 

  34. Neuromics (2012) hN2™ Human Neurons Discovery Kit. Neuromics Website. http://www.neuromics.com/ittrium/visit/A1x66x1y1x85b1x1x9cy1x622bx1x96y1x5c7fx1x82y1x5c85x1x7f. Accessed 16 Nov 2012

  35. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

    Article  PubMed  Google Scholar 

  36. Ringnér M (2008) What is principal component analysis? Nat Biotechnol 26:303–304

    Article  PubMed  Google Scholar 

  37. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57:289–300

    Google Scholar 

  38. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  CAS  Google Scholar 

  39. Spradling KD, Lumley LA, Robison CL, Meyerhoff JL, Dillman JF 3rd (2011) Transcriptional analysis of rat piriform cortex following exposure to the organophosphonate anticholinesterase sarin and induction of seizures. J Neuroinflammation 8:83

    Article  PubMed  CAS  Google Scholar 

  40. Van Vaerenbergh I, Van Lommel L, Ghislain V, In’t Veld P, Schuit F, Fatemi HM, Devroey P, Bourgain C (2009) In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression. Hum Reprod 24:1085–1091

    Article  PubMed  Google Scholar 

  41. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29

    Article  PubMed  CAS  Google Scholar 

  42. Stan A, Pielarski KN, Brigadski T, Wittenmayer N, Fedorchenko O, Gohla A, Lessmann V, Dresbach T, Gottmann K (2010) Essential cooperation of N-cadherin and neuroligin-1 in the transsynaptic control of vesicle accumulation. Proc Natl Acad Sci USA 107:11116–11121

    Article  PubMed  CAS  Google Scholar 

  43. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, Frey AS, Spektor BS, Penney EB, Schilling G, Ross CA, Borchelt DR, Tapscott SJ, Young AB, Cha JH, Olson JM (2000) Decreased expression of striatal signaling genes in a mouse model of Huntington’s disease. Hum Mol Genet 9:1259–1271

    Article  PubMed  CAS  Google Scholar 

  44. Oertle T, Klinger M, Stuermer CA, Schwab ME (2003) A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family. FASEB J 17:1238–1247

    Article  PubMed  CAS  Google Scholar 

  45. Carter CJ (2007) eIF2B and oligodendrocyte survival: where nature and nurture meet in bipolar disorder and schizophrenia? Schizophr Bull 33:1343–1353

    Article  PubMed  Google Scholar 

  46. Shi M, Bradner J, Bammler TK, Eaton DL, Zhang J, Ye Z, Wilson AM, Montine TJ, Pan C, Zhang J (2009) Identification of glutathione S-transferase pi as a protein involved in Parkinson disease progression. Am J Pathol 175:54–65

    Article  PubMed  Google Scholar 

  47. Yamada K, Nabeshima T (2003) Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci 91:267–270

    Article  PubMed  CAS  Google Scholar 

  48. Borrell-Pagès M, Zala D, Humbert S, Saudou F (2006) Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies. Cell Mol Life Sci 63:2642–2660

    Article  PubMed  Google Scholar 

  49. Cepeda C, Wu N, André VM, Cummings DM, Levine MS (2007) The corticostriatal pathway in Huntington’s disease. Prog Neurobiol 81:253–271

    Article  PubMed  CAS  Google Scholar 

  50. Di Filippo M, Tozzi A, Picconi B, Ghiglieri V, Calabresi P (2007) Plastic abnormalities in experimental Huntington’s disease. Curr Opin Pharmacol 7:106–111

    Article  PubMed  Google Scholar 

  51. Ginés S, Bosch M, Marco S, Gavaldà N, Díaz-Hernández M, Lucas JJ, Canals JM, Alberch J (2006) Reduced expression of the TrkB receptor in Huntington’s disease mouse models and in human brain. Eur J Neurosci 23:649–658

    Article  PubMed  Google Scholar 

  52. Zuccato C, Cattaneo E (2007) Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol 81:294–330

    Article  PubMed  CAS  Google Scholar 

  53. Hodges A, Strand AD, Aragaki AK, Kuhn A, Sengstag T, Hughes G, Elliston LA, Hartog C, Goldstein DR, Thu D, Hollingsworth ZR, Collin F, Synek B, Holmans PA, Young AB, Wexler NS, Delorenzi M, Kooperberg C, Augood SJ, Faull RL, Olson JM, Jones L, Luthi-Carter R (2006) Regional and cellular gene expression changes in human Huntington’s disease brain. Hum Mol Genet 15:965–977

    Article  PubMed  CAS  Google Scholar 

  54. Allen SJ, Dawbarn D (2006) Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond) 110:175–191

    Article  CAS  Google Scholar 

  55. Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 27:589–594

    Article  PubMed  CAS  Google Scholar 

  56. Hashimoto T, Bergen SE, Nguyen QL, Xu B, Monteggia LM, Pierri JN, Sun Z, Sampson AR, Lewis DA (2005) Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J Neurosci 25:372–383

    Article  PubMed  CAS  Google Scholar 

  57. Kim JM, Lee KH, Jeon YJ, Oh JH, Jeong SY, Song IS, Kim JM, Lee DS, Kim NS (2006) Identification of genes related to Parkinson’s disease using expressed sequence tags. DNA Res 13:275–286

    Article  PubMed  CAS  Google Scholar 

  58. Dedhar S, Rennie PS, Shago M, Hagesteijn CY, Yang H, Filmus J, Hawley RG, Bruchovsky N, Cheng H, Matusik RJ et al (1994) Inhibition of nuclear hormone receptor activity by calreticulin. Nature 367:480–483

    Article  PubMed  CAS  Google Scholar 

  59. Delgado IJ, Kim DS, Thatcher KN, LaSalle JM, Van den Veyver IB (2006) Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients. BMC Med Genet 7:61

    Article  PubMed  Google Scholar 

  60. Pagliuca A, Bartoli PC, Saccone S, Della Valle G, Lania L (1995) Molecular cloning of ID4, a novel dominant negative helix-loop-helix human gene on chromosome 6p21.3-p22. Genomics 27:200–203

    Article  PubMed  CAS  Google Scholar 

  61. Eastwood SL, Law AJ, Everall IP, Harrison PJ (2003) The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its synaptic pathology. Mol Psychiatry 8:148–155

    Article  PubMed  CAS  Google Scholar 

  62. Good PF, Alapat D, Hsu A, Chu C, Perl D, Wen X, Burstein DE, Kohtz DS (2004) A role for semaphorin 3A signaling in the degeneration of hippocampal neurons during Alzheimer’s disease. J Neurochem 91:716–736

    Article  PubMed  CAS  Google Scholar 

  63. Busser J, Geldmacher DS, Herrup K (1998) Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer’s disease brain. J Neurosci 18:2801–2807

    PubMed  CAS  Google Scholar 

  64. Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J Neurosci 23:2557–2563

    PubMed  CAS  Google Scholar 

  65. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98:4746–4751

    Article  PubMed  CAS  Google Scholar 

  66. Bertram L, Lill CM, Tanzi RE (2010) The genetics of Alzheimer disease: back to the future. Neuron 68:270–281

    Article  PubMed  CAS  Google Scholar 

  67. Miller JA, Oldham MC, Geschwind DH (2008) A systems level analysis of transcriptional changes in Alzheimer’s disease and normal aging. J Neurosci 28:1410–1420

    Article  PubMed  CAS  Google Scholar 

  68. Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T (2008) Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain 1:6

    Article  PubMed  Google Scholar 

  69. Tochigi M, Iwamoto K, Bundo M, Sasaki T, Kato N, Kato T (2008) Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains. Neurosci Res 60:184–191

    Article  PubMed  CAS  Google Scholar 

  70. Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z (2009) Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol 11:468–476

    Article  PubMed  CAS  Google Scholar 

  71. Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest 118:2190–2199

    PubMed  CAS  Google Scholar 

  72. Xiong H, Callaghan D, Jones A, Bai J, Rasquinha I, Smith C, Pei K, Walker D, Lue LF, Stanimirovic D, Zhang W (2009) ABCG2 is upregulated in Alzheimer’s brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Abeta(1–40) peptides. J Neurosci 29:5463–5475

    Article  PubMed  CAS  Google Scholar 

  73. Ravichandran V, Chawla A, Roche PA (1996) Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues. J Biol Chem 271:13300–13303

    Article  PubMed  CAS  Google Scholar 

  74. Hemby SE, Ginsberg SD, Brunk B, Arnold SE, Trojanowski JQ, Eberwine JH (2002) Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Arch Gen Psychiatry 59:631–640

    Article  PubMed  CAS  Google Scholar 

  75. Youdim MB, Maruyama W, Naoi M (2005) Neuropharmacological, neuroprotective and amyloid precursor processing properties of selective MAO-B inhibitor antiparkinsonian drug, rasagiline. Drugs Today (Barc) 41:369–391

    Article  CAS  Google Scholar 

  76. Weeraratna AT, Kalehua A, Deleon I, Bertak D, Maher G, Wade MS, Lustig A, Becker KG, Wood W, Walker DG, Beach TG, Taub DD (2007) Alterations in immunological and neurological gene expression patterns in Alzheimer’s disease tissues. Exp Cell Res 313:450–461

    Article  PubMed  CAS  Google Scholar 

  77. Buonanno A, Fischbach GD (2001) Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 11:287–296

    Article  PubMed  CAS  Google Scholar 

  78. Falls DL (2003) Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 284:14–30

    Article  PubMed  CAS  Google Scholar 

  79. Buonanno A (2010) The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits. Brain Res Bull 83:122–131

    Article  PubMed  CAS  Google Scholar 

  80. Göhlmann H, Talloen W (2009) Gene expression studies using Affymetrix microarrays. CRC Press, Boca Raton

    Google Scholar 

  81. Viñuela A, Snoek LB, Riksen JA, Kammenga JE (2010) Genome-wide gene expression analysis in response to organophosphorus pesticide chlorpyrifos and diazinon in C. elegans. PLoS ONE 5:e12145

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Maryanne T. Vahey and her staff of the WRAIR Vaccine Genomics Laboratory (Rockville, MD), Mr. Martin E. Nau and Dr. Zhining Wang, for their kind help in performing the microarray experiments and providing the raw data. We also thank Ms. Betty J. Benton and Dr. Brian M Keyser at USAMRICD for their help with VX exposure, and Mr. Jack Amnuaysirikul at WRAIR for his help with RNA sample preparation. This work was supported by the Defense Threat Reduction Agency (DTRA) Project No. CBS.MEDCHEM.01.10.WR.005. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the US Army or the Department of Defense.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA

    Xiugong Gao, Hsiuling Lin & Prabhati Ray

  2. Research Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USA

    Radharaman Ray

Authors
  1. Xiugong Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsiuling Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Radharaman Ray
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prabhati Ray
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Prabhati Ray.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gao, X., Lin, H., Ray, R. et al. Toxicogenomic Studies of Human Neural Cells Following Exposure to Organophosphorus Chemical Warfare Nerve Agent VX. Neurochem Res 38, 916–934 (2013). https://doi.org/10.1007/s11064-013-0996-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-013-0996-1

Keywords

Search

Navigation