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Neurochemical Journal

, Volume 8, Issue 1, pp 47–57 | Cite as

The proline-rich hypothalamic peptide is a modulator of functions of neurotrophins and neuronal activity in amyloid-induced neurodegeneration

  • M. I. Aghajanov
  • K. B. Yenkoyan
  • V. A. Chavushyan
  • J. S. Sarkissian
Experimental Articles

Abstract

On a model of neurodegeneration induced by neurotoxic peptide fragment (25–35) of β-amyloid (Aβ), we studied changes in the content of neurotrophins: insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF) in different brain areas, as well as the thymus, liver, and blood serum of rats under the influence of hypothalamic proline-rich peptide-1 (PRP-1). The effect of PRP-1 on the structural-functional state of the neurons was also studied. We showed that intramuscular injections of synthetic PRP-1 at a dose of 10 μg per 100 g of body weight for the first 9 days after intracerebroventricular administration of Aβ into the lateral brain ventricles of rats resulted in a considerable increase in the concentration of IGF-1 in all investigated brain structures, mainly, in the neocortex, hippocampus, and hypothalamus at 12 week of developing the neurodegeneration. This effect was maintained also after intramuscular administration of PRP-1 at 30 days after Aβ injection (a later date). However, as a result of PRP-1 action at early stages of the process, the tendency to decrease NGF content in the cortex, hippocampus and hypothalamus was observed. Electrophysiological and morphological studies of hippocampal neurons show, that by the 18th week after the beginning of neuro-degeneration, treatment with PRP-1 results in survival and further maintenance of cells, which indicates that PRP-1 has neuroprotective characteristics. We concluded that treatment with PRP-1 at Aβ-induced neuro-degeneration may provide normal functioning of neurons during a relatively long period of time by modulation the levels of neurotrophins both in brain and peripheria.

Keywords

proline-rich peptide insulin-like growth factor 1 nerve growth factor amyloid neurons 

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References

  1. 1.
    Walsh, D.M., Klyubin, I., and Fadeeva, J.V., Biochem. Soc. Trans., 2002, vol. 30, no. 4, pp. 552–557.PubMedCrossRefGoogle Scholar
  2. 2.
    LaFerla, F.M., Green, K.N., and Oddo, S., Nat. Rev. Neurosci, 2007, vol. 8, no. 7, pp. 499–509.PubMedCrossRefGoogle Scholar
  3. 3.
    Ondrejcak, T., Klyubin, I., Hu, N.W., Barry, A.E., Cullen, W.K., and Rowa, M.J., Neuromolecular Med, 2010, vol. 12, no. 1, pp. 13–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Rivera, E. and Noah Fulmer, A., J. Alzheimers D., vol. 8, no. 3, p. 247–268.Google Scholar
  5. 5.
    Tuszynski, M.H., Thal, L., Pay, M., Salmon, D.P, U, H.S, Bakay, R., Patel, P., Blesch, A., Vahlsing, H.L., Ho, G., Tong, G., Potkin, S.G., Fallon, J., Hansen, L., Mufson, E.J., Kordower, J.Hu., Gall, C., and Conner, J., Nat. Med, 2005, vol. 11, no. 5, pp. 551–555.PubMedCrossRefGoogle Scholar
  6. 6.
    Blesch, A., Uy, H.S., Grill, R.J., Cheng, J.G., Patterson, P.H., and Tuszynski, M.H., J. Neurosci., 1999, vol. 19, no. 9, pp. 3556–3566.PubMedGoogle Scholar
  7. 7.
    Jones, J.I. and Clemmons, D.R., Endocrinol. Rev, 1995, vol. 16, no. 1, pp. 3–34.Google Scholar
  8. 8.
    Trejo, J.L., Carro, E., and Torres-Aleman, I., J. Neurosci., 2001, vol. 21, no. 5, p. 1628–1634.PubMedGoogle Scholar
  9. 9.
    Carro, E., Trejo, J.L., Nu≠z, A., and Torres-Aleman, I., Mol. Neurobiol, 2003, vol. 27, no. 2, pp. 153–162.PubMedCrossRefGoogle Scholar
  10. 10.
    Yuan, J. and Yankner, B.A., Nature, 2000, vol. 407, no. 6805, pp. 802–809.PubMedCrossRefGoogle Scholar
  11. 11.
    Carro, E., Trejo, J., Gerber, A., Loetscher, H., Torrado, J., Metzger, F., and Torres-Aleman, I., Neurobiology of Aging, 2005, vol. 27, no. 9, pp. 1250–1257.PubMedCrossRefGoogle Scholar
  12. 12.
    Carro, E., Trejo, J.L., Gomez-Isla, T., LeRoith, D., Torres-Aleman, I., Nat. Med., 2002, vol. 8, no. 12, pp. 1390–1397.PubMedCrossRefGoogle Scholar
  13. 13.
    Trejo, J.L., Carro, E., Garcia-Galloway, E., and Torres-Aleman, I., J. Molec. Med., 2004, vol. 82, no. 3, pp. 156–162.PubMedCrossRefGoogle Scholar
  14. 14.
    Mufson, E.J., Conner, J.M., and Kordower, J.H., Neuroreport, 1995, vol. 6, no. 7, pp. 1063–1066.PubMedCrossRefGoogle Scholar
  15. 15.
    Fahnestoc, M., Scott, S.A., Jette, N., Weingartne, J.A., and Crutche, K.A., Mol. Brain Res., 1996, vol. 42, no. 1, pp. 175–178.CrossRefGoogle Scholar
  16. 16.
    Galoyan, A., Neurochem. Res, 2000, vol. 25, nos. 9–10, pp. 1343–1355.PubMedCrossRefGoogle Scholar
  17. 17.
    Galoyan A., Brain Neurosecretory Cytokines. Immune Response and Neuronal Survival, New York: Kluwer Academic, 2004, pp. 1–188.CrossRefGoogle Scholar
  18. 18.
    Gladkevich, A., Bosker, F., Korf, J., Yenkoyan, K., Vahradyan, H., and Aghajanov, M., Prog. Neuropsychopharmacol. Biol. Psychiatry, 2007, vol. 1, no. 7, pp. 1347–1355.CrossRefGoogle Scholar
  19. 19.
    Yenkoyan, K., Safaryan, K., Chavushyan, V., Meliksetyan, I., Navasardyan, G., Sarkissian, J., Galoyan, A., and Aghajanov, M., Brain Res. Bull., 2011, vol. 86, nos. 3–4, pp. 262–271.PubMedCrossRefGoogle Scholar
  20. 20.
    Galoyan, A.A., Sarkissian, J.S., Chavushyan, V.A., Meliksetyan, I.B., Avagyan, Z.E., Poghosyan, M.V., Vahradyan, H.G., Mkrtchian, H.H., and Abrahamyan, D.O., Alzheimers Dement., 2008, vol. 4, no. 5, pp. 332–344.PubMedCrossRefGoogle Scholar
  21. 21.
    Galoyan, A.A., Shakhlamov, V.A., Aghajanov, M.I., and Vahradyan, H.G. Neurochem. Res., 2004, vol. 29, no. 7, pp. 1349–1357.PubMedCrossRefGoogle Scholar
  22. 22.
    Galoyan, A.A, Sarkissian, J.S, Kipriyan, T.K., Sarkissian, E.J., Chavushyan, E.A., Sulkhanyan, R.M., Meliksetyan, I.B., Abrahamyan, S.S., Griorian, Y.Kh., Avetisyan, Z.A., and Otieva, N.A., Neurochem. Res., 2001, vol. 26, nos. 8–9, pp. 1023–1038.PubMedCrossRefGoogle Scholar
  23. 23.
    Paxinos, G. and Watson, Ch., The Rat Brain in Stereotaxic Coordinates: Compact 6th Edition, New York: Academic Press., 2005.Google Scholar
  24. 24.
    Mauric, T., Lockhar, B., Su, T., and Privat, A., Brain Res., 1996, vol. 731, nos. 1–2, pp. 249–253.CrossRefGoogle Scholar
  25. 25.
    Meliksetyan, I.B., Morfologiya, 2007, vol. 131, no. 6, pp. 77–80.Google Scholar
  26. 26.
    Palkovits, M. and Brownstein, M., Appleton and Lange, 1988, p. 223.Google Scholar
  27. 27.
    Wes, M.J., Coleman, P.D., Flood, D.G., and Troncoso, J.C., Lancet, 1994, vol. 344, no. 8925, pp. 769–772.CrossRefGoogle Scholar
  28. 28.
    Gallagher, M. and Koh, M.T., Current Opinion in Neurobiology, 2011, vol. 21, no. 6, pp. 929–934.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Yenkoyan, K., Safaryan, K., Navasardyan, G., Mkrtchyan, L., and Aghajanov, M. Neurochem. Int., 2009, vol. 54, nos. 5–6, pp. 292–298.PubMedCrossRefGoogle Scholar
  30. 30.
    Rosenfeld, R.G., Pham, H., Keller, T., Borchardt, R.T., and Pardridge, W.M. Biochem. Biophys. Res. Commun., 1987, vol. 49, no. 1, pp. 159–166.CrossRefGoogle Scholar
  31. 31.
    Frank, H.J., Pardridg, W.M., Morri, W.L., Rosenfeld, R.G., and Choi, T.B. Diabetes, 1986, vol. 5, no. 6, pp. 654–661.CrossRefGoogle Scholar
  32. 32.
    Tham, A., Nordberg, A., Grissom, F.E., Carlsson-Skwirut, C., Viitanen, M., and Sara, V.R., J. Neural. Transm. Park Dis. Dement. Sect, 1993, vol. 5, no. 3, p. 165–176.PubMedCrossRefGoogle Scholar
  33. 33.
    Torres-Aleman, I., Mol. Neurobiol, 2000, vol. 21, no. 3, pp. 153–160.PubMedCrossRefGoogle Scholar
  34. 34.
    Nuñez, A., Carro, E., and Torres-Aleman, I., J. Neurophysiol., 2003, vol. 89, no. 6, pp. 3008–3017.PubMedCrossRefGoogle Scholar
  35. 35.
    Nuñez, A. and Buño, W., Eur. J. Neurosci, 1999, vol. 11, no. 6, pp. 186–1876.CrossRefGoogle Scholar
  36. 36.
    Hoffman, D.A., Magee, J.C., Colbert, C.M., and Johnston, D., Nature, 1977, vol. 387, no. 6636, pp. 869–875.Google Scholar
  37. 37.
    Sofroniew, M.V., Howe, C.L., and Mobley, W.C., Annu. Rev. Neurosci., 2001, vol. 24. pp. 1217–1281.PubMedCrossRefGoogle Scholar
  38. 38.
    Jung, KM., Tan, S., Landman, N., Petrova, K., Murray, S., Lewis, R., Kim, P.K., Kim, D.S., Ryu, S.H., Chao, M.V., and Kim, T.W., J. Biol. Chem., 2003, vol. 278, no. 43, pp. 42161–42169.PubMedCrossRefGoogle Scholar
  39. 39.
    Roux, P.P. and Barker, P.A., Prog. Neurobiol, 2002, vol. 67, no. 3, pp. 203–233.PubMedCrossRefGoogle Scholar
  40. 40.
    Rabizadeh, S. and Bredesen, D.E., Cytokine Growth Factor Rev, 2003, vol. 14, nos. 3–4, pp. 225–239.PubMedCrossRefGoogle Scholar
  41. 41.
    Hazari, M.S., Pan, J.H., and Myers, A.C., Am. J. Physiology Lung Cell Mol. Physiol., 2007, vol. 292, no. 4, pp. L992–L1001.CrossRefGoogle Scholar
  42. 42.
    Wasling, P., Daborg, J., Riebe, I., Andersson, M., Portelius, E., Blennow, K., Hanse, E., and Zetterberg, H., J. Alzheimers D., vol. 16, no. 1, pp. 1–14.Google Scholar
  43. 43.
    Palop, J.J. and Mucke, L., Nature Neuroscience, 2010, vol. 13, no. 7, pp. 812–818.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Palop, J.J., Chin, J., Roberson, E.D., Wang, J., Thwin, M.T., Bien-Ly, N., Yoo, J., Ho, K.O., Yu, G.Q., Kreitzer, A., Finkbeiner, S., Noebels, J.L., and Mucke, L., Neuron, 2007, vol. 55, no. 5, pp. 697–711.PubMedCrossRefGoogle Scholar
  45. 45.
    Bruno, M.A., Leon, W.C., Fragoso, G., Mushynski, W.E., Almazan, G., and Cuello, A.C., J. Neuropathol. Exp. Neurol., 2009, vol. 68, no. 8, pp. 857–869.PubMedCrossRefGoogle Scholar
  46. 46.
    Thoenen, H., Prog. Brain Res., 2000, vol. 128, pp. 183–191.PubMedCrossRefGoogle Scholar
  47. 47.
    Paredes, D., Granholm, A.C., and Bickford, P.C., Brain Res., 2007, vol. 1141, pp. 56–64.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Auld, D.S., Mennicken, F., and Quirion, R., J. Neurosci., 2001, vol. 21, no. 10, p. 3375–3382.PubMedGoogle Scholar
  49. 49.
    Kelsch, W., Hormuzdi, S., Straube, E., Lewen, A., Monyer, H., and Misgeld, U., J. Neurosci., 2001, vol. 21, no. 21, pp. 8339–8347.PubMedGoogle Scholar
  50. 50.
    Gonzalez de la Vega, A., Buño, W., Pons, S., Garcia-Calderat, M.S., Garcia-Galloway, E., and Torres-Aleman, I., Neuroreport, 2001, vol. 12, no. 6, pp. 1293–1296.PubMedCrossRefGoogle Scholar
  51. 51.
    Wan, Q., Xiong, Z.G., and Man, H.Y., Nature, 1997, vol. 388, no. 6643, pp. 686–690.PubMedCrossRefGoogle Scholar
  52. 52.
    Fadool, D.A., Tucker, K., Phillips, J.J., and Simmen, J.A., J. Neurophysiol., 2000, vol. 83, no. 4, pp. 2332–2348.PubMedGoogle Scholar
  53. 53.
    Carro, E., Nuñez, A., Busiguina, S., and Torres-Aleman, I., J. Neurosci., 2000, vol. 20, no. 8, pp. 2926–2933.PubMedGoogle Scholar
  54. 54.
    Garcia-Galloway, E., Arango, C., Pons, S., and Torres-Aleman, I., Mol. Cell. Neurosci., 2003, vol. 24, no. 4, pp. 1027–1037.PubMedCrossRefGoogle Scholar
  55. 55.
    Xie L., Helmerhorst, E., Taddei, K., Plewright, B., Van Bronswijk, W., and Martins, R., J. Neurosci., 2002, vol. 22, no. 10 (RC221), pp. 1–5.Google Scholar
  56. 56.
    Ullrich, A., Gray, A., Tam, A.W., Yang-Feng, T., Tsubokawa, M., Collins, C., Henzel, W., Le Bon, T., Kathuria, S., and Chen, E., EMBO J., 1986, vol. 5, no. 10, pp. 2503–2512.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Gasparini, L., Netzer, W.J., Greengard, P., and Xu, H., Trends. Pharmacol. Sci., 2002, vol. 23, no. 6, pp. 288–293.PubMedCrossRefGoogle Scholar
  58. 58.
    Jain, S., Golde, D.W., Bailey, R., and Geffner, M.E., Endocr. Rev., 1988, vol. 19, no. 5, pp. 625–646.Google Scholar
  59. 59.
    Buhler, A.V. and Dunwiddie, T.V., J. Neurophysiol., 2002, vol. 87, no. 1, pp. 548–557.PubMedGoogle Scholar
  60. 60.
    Ge, S. and Dani, J.A., J. Neurosci, 2005, vol. 25, no. 26, pp. 6084–6091.PubMedCrossRefGoogle Scholar
  61. 61.
    Bak, L.K., Schousboe, A., and Waagepetersen, H.S., J. Neurochem., 2006, vol. 98, no. 3, pp. 641–653.PubMedCrossRefGoogle Scholar
  62. 62.
    Mathews, G.C. and Diamond, J.S., J. Neurosci., 2003, vol. 23, no. 6, pp. 2040–2048.PubMedGoogle Scholar
  63. 63.
    Mann, E.O. and Paulsen, O., Trends Neurosci., 2007, vol. 30, no. 7, pp. 343–349.PubMedCrossRefGoogle Scholar
  64. 64.
    Rissman, R.A., De Blas, A.L., and Armstrong, D.M., J. Neurochem., 2007, vol. 103, no. 4, pp. 1285–1292.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • M. I. Aghajanov
    • 1
  • K. B. Yenkoyan
    • 1
    • 3
  • V. A. Chavushyan
    • 2
  • J. S. Sarkissian
    • 2
  1. 1.Heratsi Yerevan State Medical UniversityYerevanArmenia
  2. 2.Orbeli Institute of PhysiologyNational Academy of SciencesYerevanArmenia
  3. 3.YerevanArmenia

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