Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y

  • R. Constantinescu
  • A. T. Constantinescu
  • H. Reichmann
  • B. Janetzky
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 72)


Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder in industrialized countries. Present cell culture models for PD rely on either primary cells or immortal cell lines, neither of which allow for long-term experiments on a constant population, a crucial requisite for a realistic model of slowly progressing neurodegenerative diseases.


Dopaminergic neurons mitotic inhibitors neuronal differentiation neuronal markers perfusion culture retinoic acid 


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  1. Barzilai A, Melamed E, Shirvan A (2001) Is there a rationale for neuro-protection against dopamine toxicity in Parkinson’s disease? Cell Mol Neurobio 121: 215–235CrossRefGoogle Scholar
  2. Biedler JL, Helson L, Spengler BA (1973) Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res 33: 2643–2652PubMedGoogle Scholar
  3. Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS (1978) Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38: 3751–3757PubMedGoogle Scholar
  4. Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101: 1371–1378PubMedCrossRefGoogle Scholar
  5. Blander G, de Oliveira RM, Conboy CM, Haigis M, Guarente L (2003) Superoxide dismutase 1 knock-down induces senescence in human fibroblasts. J Biol Chem 278: 38966–38969PubMedCrossRefGoogle Scholar
  6. Bove J, Prou D, Perier C, Przedborski S (2005) Toxin-induced models of Parkinson’s disease. NeuroRx 2: 484–494PubMedCrossRefGoogle Scholar
  7. Cajal SR y (1928) Degeneration and regeneration of the nervous system. University Press, LondonGoogle Scholar
  8. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39: 889–909PubMedCrossRefGoogle Scholar
  9. Duggal N, Hammond RR (2002) Nestin expression in ganglioglioma. Exp Neurol 174: 89–95PubMedCrossRefGoogle Scholar
  10. Edsjo A, Lavenius E, Nilsson H, Hoehner JC, Simonsson P, Culp LA, Martinsson T, Larsson C, Pahlman S (2003) Expression of trkB in human neuroblastoma in relation to MYCN expression and retinoic acid treatment. Lab Invest 83: 813–823PubMedGoogle Scholar
  11. Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Cena V, Gallego C, Cornelia JX (2000) Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 75: 991–1003PubMedCrossRefGoogle Scholar
  12. Farooqui SM (1994) Induction of adenylate cyclase sensitive dopamine D2-receptors in retinoic acid induced differentiated human neuro-blastoma SH-SY5Y cells. Life Sci 55: 1887–1893PubMedCrossRefGoogle Scholar
  13. Gaardsvoll H, Obendorf D, Winkler H, Bock E (1988) Demonstration of immunochemical identity between the synaptic vesicle proteins synaptin and synaptophysin/p38. FEBS Lett 242: 117–120PubMedCrossRefGoogle Scholar
  14. Gage FH (2002) Neurogenesis in the adult brain. J Neurosci 22: 612–613PubMedGoogle Scholar
  15. Gates MA, Torres EM, White A, Fricker-Gates RA, Dunnett SB (2006) Re-examining the ontogeny of substantia nigra dopamine neurons. Eur J Neurosci 23: 1384–1390PubMedCrossRefGoogle Scholar
  16. Gille G, Rausch WD, Hung ST, Moldzio R, Ngyuen A, Janetzky B, Engfer A, Reichmann H (2002) Protection of dopaminergic neurons in primary culture by lisuride. J Neural Transm 109: 157–169PubMedCrossRefGoogle Scholar
  17. Hashemi SH, Li JY, Ahlman H, Dahlstrom A (2003) SSR2(a) receptor expression and adrenergic/cholinergic characteristics in differentiated SH-SY5Y cells. Neurochem Res 28: 449–460PubMedCrossRefGoogle Scholar
  18. Herman GE (2002) Mouse models of human disease: lessons learned and promises to come. ILAR J 43: 55–56PubMedGoogle Scholar
  19. Laifenfeld D, Klein E, Ben Shachar D (2002) Norepinephrine alters the expression of genes involved in neuronal sprouting and differentiation: relevance for major depression and antidepressant mechanisms. J Neurochem 83: 1054–1064PubMedCrossRefGoogle Scholar
  20. Lee JE, Hollenberg SM, Snider L, Turner DL, Lipnick N, Weintraub H (1995) Conversion of xenopus ectoderm into neurons by neurod, a basic helix-loop-helix protein. Science 268: 836–844PubMedCrossRefGoogle Scholar
  21. Lee MK, Tuttle JB, Rebhun LI, Cleveland DW, Frankfurter A (1990) The expression and posttranslational modification of a neuron-specific beta-tubulin isotype during chick embryogenesis. Cell Motil Cytoskeleton 17: 118–132PubMedCrossRefGoogle Scholar
  22. Ma Q, Kintner C, Anderson DJ (1996) Identification of neurogenin, a vertebrate neuronal determination gene. Cell 87: 43–52PubMedCrossRefGoogle Scholar
  23. Maden M, Hind M (2003) Retinoic acid, a regeneration-inducing molecule. Dev Dyn 226: 237–244PubMedCrossRefGoogle Scholar
  24. Maruyama W, Benedetti MS, Takahashi T, Naoi M (1997) A neurotoxin N-methyl(R)salsolinol induces apoptotic cell death in differentiated human dopaminergic neuroblastoma SH-SY5Y cells. Neurosci Lett 232: 147–150PubMedCrossRefGoogle Scholar
  25. Melino G, Thiele CJ, Knight RA, Piacentini M (1997) Retinoids and the control of growth/death decisions in human neuroblastoma cell lines. J Neurooncol 31: 65–83PubMedCrossRefGoogle Scholar
  26. Minuth WW, Schumacher K, Strehl R, Kloth S (2000) Physiological and cell biological aspects of perfusion culture technique employed to generate differentiated tissues for long term biomaterial testing and tissue engineering. J Biomater Sci Polym Ed 11: 495–522PubMedCrossRefGoogle Scholar
  27. Minuth WW, Steiner P, Strehl R, Schumacher K, de Vries U, Kloth S (1999) Modulation of cell differentiation in perfusion culture. Exp Nephrol 7: 394–406PubMedCrossRefGoogle Scholar
  28. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116: 201–211PubMedGoogle Scholar
  29. Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278: 58–63PubMedCrossRefGoogle Scholar
  30. Nicolini G, Miloso M, Zoia C, Di Silvestro A, Cavaletti G, Tredici G (1998) Retinoic acid differentiated SH-SY5Y human neuroblastoma cells: an in vitro model to assess drug neurotoxicity. Anticancer Res 18: 2477–2481PubMedGoogle Scholar
  31. Pahlman S, Hoehner JC, Nanberg E, Hedborg F, Fagerstrom S, Gestblom C, Johansson I, Larsson U, Lavenius E, Ortoft E, Soderholm H (1995) Differentiation and Survival Influences of Growth-Factors in Human Neuroblastoma. Eur J Cancer 31A: 453–458PubMedCrossRefGoogle Scholar
  32. Pleasure SJ, Page C, Lee VM (1992) Pure, postmitotic, polarized human neurons derived from NTera 2 cells provide a system for expressing exogenous proteins in terminally differentiated neurons. J Neurosci 12: 1802–1815PubMedGoogle Scholar
  33. Presgraves SP, Ahmed T, Borwege S, Joyce JN (2004) Terminally differentiated SH-SY5Y cells provide a model system for studying neuro-protective effects of dopamine agonists. Neurotox Res 5: 579–598PubMedCrossRefGoogle Scholar
  34. Rakic P (2002) Adult neurogenesis in mammals: an identity crisis. J Neurosci 22: 614–618PubMedGoogle Scholar
  35. Rasband WS (2006) Image J. U. S. National Institutes of Health, Bethesda, Maryland, USA,
  36. Rebhan M, Vacun G, Bayreuther K, Rosner H (1994) Altered ganglioside expression by SH-SY5Y cells upon retinoic acid-induced neuronal differentiation. Neuroreport 5: 941–944PubMedCrossRefGoogle Scholar
  37. Ross RA, Spengler BA, Biedler JL (1983) Coordinate morphological and biochemical interconversion of human neuroblastoma cells. J Natl Cancer Inst 71: 741–747PubMedGoogle Scholar
  38. Sherer TB, Trimmer PA, Borland K, Parks JK, Bennett JP Jr, Tuttle JB (2001) Chronic reduction in complex I function alters calcium signaling in SH-SY5Y neuroblastoma cells. Brain Res 891: 94–105PubMedCrossRefGoogle Scholar
  39. Singh US, Pan J, Kao YL, Joshi S, Young KL, Baker KM (2003) Tissue transglutaminase mediates activation of RhoA and MAP kinase pathways during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. J Biol Chem 278: 391–399PubMedCrossRefGoogle Scholar
  40. Storch A, Ludolph AC, Schwarz J (2004) Dopamine transporter: involvement in selective dopaminergic neurotoxicity and degeneration. J Neural Transm 111: 1267–1286PubMedCrossRefGoogle Scholar
  41. Timpl R, Brown JC (1994) The laminins. Matrix Biol 14: 275–281PubMedCrossRefGoogle Scholar
  42. Willets JM, Lambert DG, Lunec J, Griffiths HR (1995) Studies on the neurotoxicity of 6,7-dihydroxy-l-methyl-l,2,3,4-tetrahydroiso-quinoline(salsolinol) in SH-SY5Y cells. Eur J Pharmacol 293: 319–326PubMedCrossRefGoogle Scholar
  43. Wood JG, Mirra SS, Pollock NJ, Binder LI (1986) Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau). Proc Natl Acad Sci USA 83: 4040–4043PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • R. Constantinescu
    • 1
  • A. T. Constantinescu
    • 2
  • H. Reichmann
    • 1
  • B. Janetzky
    • 1
  1. 1.Department of Neurology, Faculty of Medicine Carl Gustav CarusDresden University of TechnologyDresdenGermany
  2. 2.Max-Planck-Institute of Molecular Cell Biology and GeneticsDresdenGermany

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