Neurodegenerative Diseases

Original Paper

Neuroprotective Effect of Neuropeptide Y against Beta-Amyloid 25–35 Toxicity in SH-SY5Y Neuroblastoma Cells Is Associated with Increased Neurotrophin Production

Croce N.a, b · Dinallo V.b · Ricci V.a · Federici G.a, b · Caltagirone C.a, c · Bernardini S.b · Angelucci F.a

Author affiliations

aIRCCS Santa Lucia Foundation and bDepartment of Internal Medicine and cDepartment of Neuroscience, Tor Vergata University, Rome, Italy

Keywords: Neuropeptide YBeta-amyloidNeuroblastomaNeurotrophins

Related Articles for ""
Neurodegenerative Dis 2011;8:300–309
https://doi.org/10.1159/000323468

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 01, 2010
Accepted: September 12, 2010
Published online: February 23, 2011
Issue release date: June 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Abstract

Background: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer’s disease (AD). Among them, neuropeptide Y (NPY) is a small peptide widely distributed throughout the brain, where it serves as a neurotransmitter and/or a modulator of several neuroendocrine functions. More recently, NPY has generated interest because of its role in neuroprotection against excitotoxicity and modulation of neurogenesis. Interestingly, these effects are also influenced by neurotrophins, critical molecules for the function and survival of neurons that degenerate in AD. Objective: Our purpose was to investigate whether NPY might be a neuroprotective agent in AD and whether neurotrophins are involved in NPY-induced neuroprotection. Methods: To test this hypothesis, we exposed the SH-SY5Y neuroblastoma cell line to toxic concentrations of β-amyloid (Aβ) peptide fragment 25–35 (Aβ25–35) and measured cell survival and neurotrophin expression before and after a preincubation with NPY in the growth medium. Results: Our results demonstrated that preincubation with NPY prevented cell loss due to the toxic effect of Aβ25–35. Moreover, while intracellular production of nerve growth factor and brain-derived neurotrophic factor were reduced by Aβ, NPY restored or even increased neurotrophin protein and mRNA in SH-SY5Y cells. Conclusion: In conclusion, this study demonstrates that NPY increases the survival of SH-SY5Y neuroblastoma cells and counteracts the toxic effect of Aβ. In addition, NPY restores the neurotrophin levels in these cells. Although preliminary, these observations might be useful to understand the pathology of Alzheimer’s and/or develop new therapeutic strategies.

© 2011 S. Karger AG, Basel



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References

  1. Blennow K, de Leon MJ, Zetterberg H: Alzheimer’s disease. Lancet 2006;368:387–403.
    External Resources
  2. Selkoe DJ: Toward a comprehensive theory for Alzheimer’s disease – Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid β-protein. Ann NY Acad Sci 2000;924:17–25.
    External Resources
  3. Colton CA, Vitek MP: NPY and chronic neurodegenerative disease: NPY family of peptides in neurobiology, cardiovascular and metabolic disorders from genes to therapeutics. J Neural Transm 2006;113:231–238.
    External Resources
  4. Gutman AR, Yang Y, Ressler KJ, Davis M: The role of neuropeptide Y in the expression and extinction of fear-potentiated startle. J Neurosci 2008;28:12682–12690.
    External Resources
  5. El Bahh B, Balosso S, Hamilton T, Herzog H, Beck-Sickinger AG, Sperk G, Gehlert DR, Vezzani A, Colmers WF: The anti-epileptic actions of neuropeptide Y in the hippocampus are mediated by Y and not Y receptors. Eur J Neurosci 2005;22:1417–1430.
    External Resources
  6. Goyal SN, Upadhya MA, Kokare DM, Bhisikar SM, Subhedar NK: Neuropeptide Y modulates the antidepressant activity of imipramine in olfactory bulbectomized rats: involvement of NPY Y1 receptors. Brain Res 2009;1266:45–53.
    External Resources
  7. Martel JC, Alagar R, Robitaille Y, Quirion R: Neuropeptide Y receptor binding sites in human brain: possible alteration in Alzheimer’s disease. Brain Res 1990;519:228–235.
    External Resources
  8. Koide S, Onishi H, Hashimoto H, Kai T, Yamagami S: Plasma neuropeptide Y is reduced in patients with Alzheimer’s disease. Neurosci Lett 1995;198:149–151.
    External Resources
  9. Alom J, Galard R, Catalan R, Castellanos JM, Schwartz S, Tolosa E: Cerebrospinal fluid neuropeptide Y in Alzheimer’s disease. Eur Neurol 1990;30:207–210.
    External Resources
  10. Rose JB, Crews L, Rockenstein E, Adame A, Mante M, Hersh LB, Gage FH, Spencer B, Potkar R, Marr RA, Masliah E: Neuropeptide Y fragments derived from neprilysin processing are neuroprotective in a transgenic model of Alzheimer’s disease. J Neurosci 2009;29:1115–1125.
    External Resources
  11. Silva AP, Pinheiro PS, Carvalho AP, Carvalho CM, Jakobsen B, Zimmer J, Malva JO: Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures. FASEB J 2003;17:1118–1120.
    External Resources
  12. Decressac M, Wright B, David B, Tyers P, Jaber M, Barker RA, Gaillard A: Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis. Hippocampus 2010, Epub ahead of print.
  13. Howell OW, Silva S, Scharfman HE, Sosunov AA, Zaben M, Shatya A, McKhann G 2nd, Herzog H, Laskowski A, Gray WP: Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus. Neurobiol Dis 2007;26:174–188.
    External Resources
  14. Howell OW, Doyle K, Goodman JH, Scharfman HE, Herzog H, Pringle A, Beck-Sickinger AG, Gray WP: Neuropeptide Y stimulates neuronal precursor proliferation in the post-natal and adult dentate gyrus. J Neurochem 2005;93:560–570.
    External Resources
  15. Querfurth HW, LaFerla FM: Alzheimer’s disease. N Engl J Med 2010;362:329–344.
    External Resources
  16. Huang EJ, Richardt LF: Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001;24:677–736.
    External Resources
  17. Cuello AC, Bruno MA, Allard S, Leon W, Iulita MF: Cholinergic involvement in Alzheimer’s disease: a link with NGF maturation and degradation. J Mol Neurosci 2010;40:230–235.
    External Resources
  18. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH: Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 2009;15:331–337.
    External Resources
  19. Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J, Kilbridge JF, Carlson EJ, Epstein CJ, Mobley WC: Failed retrograde transport of NGF in a mouse model of Down’s syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci USA 2001;98:10439–10444.
    External Resources
  20. Tuszynski MH: Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 2007;21:179–189.
    External Resources
  21. Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M: Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Brain Res Mol Brain Res 1997;49:71–81.
    External Resources
  22. Peng S, Wuu J, Mufson EJ, Fahnestock M: Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem 2005;93:1412–1421.
    External Resources
  23. Angelucci F, Spalletta G, di Iulio F, Ciaramella A, Salani F, Colantoni L, Varsi AE, Gianni W, Sancesario G, Caltagirone C, Bossù P: Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients are characterized by increased BDNF serum levels. Curr Alzheimer Res 2010;7:15–20.
    External Resources
  24. Yoshimura R, Ito K, Endo Y: Differentiation/maturation of neuropeptide Y neurons in the corpus callosum is promoted by brain-derived neurotrophic factor in mouse brain slice cultures. Neurosci Lett 2009;450:262–265.
    External Resources
  25. Medina-Ortiz WE, García-Arrarás JE: Differential regulation of NPY mRNA expression in embryonic sympathetic and chromaffin cultures by NGF. Brain Res Dev Brain Res 2000;119:155–158.
    External Resources
  26. Påhlman S, Hoehner JC, Nånberg E, Hedborg F, Fagerström S, Gestblom C, Johansson I, Larsson U, Lavenius E, Ortoft E, Soderholm H: Differentiation and survival influences of growth factors in human neuroblastoma. Eur J Cancer 1995;31A:453–458.
    External Resources
  27. Påhlman S, Ruusala AI, Abrahamsson L, Mattsson ME, Esscher T: Retinotic acid-induced differentiation of cultured human neuroblastoma cells: a comparison with phorbol ester-induced differentiation. Cell Differ 1984;14:135–144.
    External Resources
  28. Cheung YT, Lau WK, Yu MS, Lai CS, Yeung SC, So KF, Chang RC: Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology 2009;30:127–135.
    External Resources
  29. Hansel DE, Eipper BA, Ronnett GV: Neuropeptide Y functions as a neuroproliferative factor. Nature 2001;410:940–944.
    External Resources
  30. Zukowska-Grojec Z, Pruszczyk P, Colton C, Yao J, Shen GH, Myers AK, Wahlestedt C: Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells. Peptides 1993;14:263–268.
    External Resources
  31. Protas L, Qu J, Robinson RB: Neuropeptide Y: neurotransmitter or trophic factor in the heart? News Physiol Sci 2003;18:181–185.
    External Resources
  32. Zhao S, Fernald RD: Comprehensive algorhythm for quantitative real-time polymerase chain reaction. J Comput Biol 2005;12:1045–1062.
  33. Millucci L, Ghezzi L, Bernardini G, Santucci A: Conformations and biological activities of amyloid β peptide 25–35. Curr Protein Pept Sci 2010;11:54–67.
    External Resources
  34. Stanley BG, Leibowitz SF: Neuropeptide Y: stimulation of feeding and drinking by injection into the paraventricular nucleus. Life Sci 1984;35:2635–2642.
    External Resources
  35. Flood JF, Hernandez EN, Morley JE: Modulation of memory processing by neuropeptide Y. Brain Res 1987;421:280–290.
    External Resources
  36. Redrobe JP, Dumont Y, St-Pierre JA, Quirion R: Multiple receptors for neuropeptide Y in the hippocampus: putative roles in seizures and cognition. Brain Res 1999;848:153–166.
    External Resources
  37. Vezzani A, Sperk G: Overexpression of NPY and Y2 receptors in epileptic brain tissue: an endogenous neuroprotective mechanism in temporal lobe epilepsy? Neuropeptides 2004;38:245–252.
    External Resources
  38. Bastianetto S, Ramassamy C, Doré S, Christen Y, Poirier J, Quirion R: The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by β-amyloid,. Eur J Neurosci 2000;12:1882–1890.
    External Resources
  39. Doré S, Kar S, Quirion R: Insulin-like growth factor I protects and rescues hippocampal neurons against β-amyloid- and human amylin-induced toxicity, Proc Natl Acad Sci USA 1997;94:4772–4777.
    External Resources
  40. Del Mar Martinez-Senac M, Villalain J, Gomez-Fernandez JC: Structure of the Alzheimer β-amyloid peptide (25–35) and its interaction with negatively charged phospholipid vesicles. Eur J Biochem 1999;265:744–753.
    External Resources
  41. Iversen LL, Mortishire-Smith RJ, Pollack SJ, Shearman MS: The toxicity in vitro of β-amyloid protein. Biochem J 1995;311:1–16.
    External Resources
  42. Pike CJ, Walencewicz-Wasserman AJ, Kosmoski J, Cribbs DH, Glabe CG, Cotman CW: Structure-activity analyses of β-amyloid peptides: contributions of the β 25–35 region to aggregation and neurotoxicity. J Neurochem 1995;64:253–265.
    External Resources
  43. Shearman MS, Ragan CI, Iversen LL: Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of β-amyloid-mediated cell death. Proc Natl Acad Sci USA 1994;91:1470–1474.
    External Resources
  44. Terzi E, Holzemann G, Seelig J: Reversible random coil-β-sheet transition of the Alzheimer β-amyloid fragment (25–35). Biochemistry 1994;33:1345–1350.
    External Resources
  45. Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, Floyd RA, Butterfield DA: A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 1994;91:3270–3274.
    External Resources
  46. Parks JK, Smith TS, Trimmer PA, Bennett JP Jr, Parker WD Jr: Neurotoxic Aβ peptides increase oxidative stress in vivo through NMDA-receptor and nitricoxide- synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J Neurochem 2001;76:1050–1056.
    External Resources
  47. Albensi BC: The NMDA receptor/ion channel complex: a drug target for modulating synaptic plasticity and excitotoxicity. Curr Pharm Des 2007;13:3185–3194.
    External Resources
  48. Colmers WF, Bleakman D: Effects of neuropeptide Y on the electrical properties of neurons. Trends Neurosci 1994;17:373–379.
    External Resources
  49. Greber S, Schwarzer C, Sperk G: Neuropeptide Y inhibits potassium-stimulated glutamate release through Y2 receptors in rat hippocampal slices in vitro. Br J Pharmacol 1994;113:737–740.
    External Resources
  50. Qian J, Colmers WF, Saggau P: Inhibition of synaptic transmission by neuropeptide Y in rat hippocampal area CA1: modulation of presynaptic Ca2+ entry. J Neurosci 1997;17:8169–8177.
    External Resources
  51. Silva AP, Carvalho AP, Carvalho CM, Malva JO: Modulation of intracellular calcium changes and glutamate release by neuropeptide Y1 and Y2 receptors in the rat hippocampus: differential effects in CA1, CA3 and dentate gyrus. J Neurochem 2001;79:286–296.
    External Resources
  52. Silva AP, Carvalho AP, Carvalho CM, Malva JO: Functional interaction between neuropeptide Y receptors and modulation of calcium channels in the rat hippocampus. Neuropharmacology 2003;44:282–292.
    External Resources
  53. Smiałowska M, Domin H, Zieba B, Koźniewska E, Michalik R, Piotrowski P, Kajta M: Neuroprotective effects of neuropeptide Y-Y2 and Y5 receptor agonists in vitro and in vivo. Neuropeptides 2009:235–249.
    External Resources
  54. Xapelli S, Silva AP, Ferreira R, Malva JO: Neuropeptide Y can rescue neurons from cell death following the application of an excitotoxic insult with kainate in rat organotypic hippocampal slice cultures. Peptides 2007;28:288–294.
    External Resources
  55. Vezzani A, Sperk G, Colmers WF, Neuropeptide Y: emerging evidence for a functional role in seizure modulation.Trends Neurosci 1999;22:25–30.
    External Resources
  56. Sperk G, Hamilton T, Colmers WF: Neuropeptide Y in the dentate gyrus. Prog Brain Res 2007;163:285–297.
    External Resources
  57. McQuiston AR, Petrozzino JJ, Connor JA, Colmers WF: Neuropeptide Y1 receptors inhibit N-type calcium currents and reduce transient calcium increases in rat dentate granule cells. J Neurosci 1996;16:1422–1429.
    External Resources
  58. Kofler N, Kirchmair E, Schwarzer C, Sperk G: Altered expression of NPY-Y1 receptors in kainic acid induced epilepsy in rats. Neurosci Lett 1997;230:129–132.
    External Resources
  59. Garzon DJ, Fahnestock M: Oligomeric amyloid decreases basal levels of brain-derived neurotrophic factor (BDNF) mRNA via specific downregulation of BDNF transcripts IV and V in differentiated human neuroblastoma cells. J Neurosci 2007;27:2628–2635.
    External Resources
  60. Liu H, Liu Z, Xu X, Yang X, Wang H, Li Z: Nerve growth factor regulates galanin and neuropeptide Y expression in primary cultured superior cervical ganglion neurons. Pharmazie 2010;65:219–223.
    External Resources
  61. Wirth MJ, Patz S, Wahle P: Transcellular induction of neuropeptide Y expression by NT4 and BDNF. Proc Natl Acad Sci USA 2005;102:3064–3069.
    External Resources
  62. Xapelli S, Bernardino L, Ferreira R, Grade S, Silva AP, Salgado JR, Cavadas C, Grouzmann E, Poulsen FR, Jakobsen B, Oliveira CR, Zimmer J, Malva JO: Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity: a role for microglia. Eur J Neurosci 2008;27:2089–2102.
    External Resources
  63. Kastin AJ, Akerstrom V: Nonsaturable entry of neuropeptide Y into brain. Am J Physiol 1999;276:E479–E482.
    External Resources
  64. Kastin AJ, Pan W: Blood-brain barrier and feeding: regulatory roles of saturable transport systems for ingestive peptides. Curr Pharm Des 2008;14:1615–1619.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 01, 2010
Accepted: September 12, 2010
Published online: February 23, 2011
Issue release date: June 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

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2011, Vol.8, No. 5

June 2011

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