Anatomical and Functional Characteristics of Transplanted Monoaminergic Neurons in Paraplegic Rats

  • Minerva Giménez y Ribotta
  • Christelle Roudet
  • Alain Privat
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 429)


The transplantation of embryonic tissue in the CNS has been used as a strategy for reducing deficits associated with degenerative diseases and for promoting functional recovery after brain or spinal cord injury (Fisher and Gage, 1993; Freed, 1993; Goldberger et al., 1993a; Nishino 1993).


Spinal Cord Spinal Cord Injury Intact Animal Spinal Cord Transection Monoaminergic Neuron 
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  1. Bernstein, J.J., and Bernstein, M.E. (1971). Axonal regeneration and formation of synapses proximal to the site of the lesion following hemisection of the spinal cord. Exp. Neural., 30: 336–351.CrossRefGoogle Scholar
  2. Bernstein,.I.J., and Bernstein, M.E. (1973). Neuronal alteration and reinnervation following axonal regeneration and sprouting in mammalian spinal cord. Brain Behan Evol., 8: 135–161.CrossRefGoogle Scholar
  3. Björklund, A., Nornes, H., and Gage, F.H. (1986). Cell suspension grafts of noradrenergic locus coeruleus neurons in rat hippocampus and spinal cord: Reinnervation and transmitter turnover. Neuroscience, 18: 685–698.PubMedCrossRefGoogle Scholar
  4. Björklund, A. and Skagerberg, G. (1982). Descending monoaminergic projections to the spinal cord. In B. Sjölund and A. Björklund (Eds), Brainstem Control of Spinal Mechanisms, Elsevier, Amsterdam. pp. 55–85.Google Scholar
  5. Björklund, A., Stenevi, U., and Dunnett, S.B. (1983). Transplantation of brainstem monoaminergic `command’ systems: models for functional reactivation of damaged CNS circuitries. In C.C. Kao, R.P. Bunge, and P.J. Reier (Eds), Spinal Cord Reconstruction, Raven Press, New York. pp. 397–413.Google Scholar
  6. Bregman, B.S., Bernstein-Goral, H., and Kunkel-Bagden, E. (1991). CNS transplants promote anatomical plasticity and recovery of function after spinal cord injury. Rest. Neural. Neurosci., 2: 327–338.Google Scholar
  7. Bregman, 13.S. Kunkel-Bagden, E., Reier, P.J., Dai, H.N., Mc Atee, M., and Gao. D. (1993). Recovery of function after spinal cord injury: Mechanisms underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rats. Exp. Neural., 123: 3–16.CrossRefGoogle Scholar
  8. Buchanan. J.T., and Nornes, H.O. (1986). Transplants of embryonic brainstem containing the locus coeruleus into spinal cord enhance the hindlimb flexion reflex in adult rats. Brain Res., 381: 225–236.CrossRefGoogle Scholar
  9. Commissiong, J.W. (1983). Fetal locus coeruleus transplanted into the transected spinal cord of the adult rat. Brain Res., 271: 174–179.PubMedCrossRefGoogle Scholar
  10. Commissiong, J.W. (1984). Fetal locus coeruleus transplanted into the transected spinal cord of the adult rat: some observations and implications. Neuroscience, 12: 839–853.PubMedCrossRefGoogle Scholar
  11. Connor, H.E., Drew, G.M., Finch, L. and Hicks, P.E. (1981). Pharmacological characteristics of spinal a-adrenoceptors in rats. J$14uton. Phurmacol. l: 149–156.Google Scholar
  12. Cotman, C.W., Nieto-Sampedro, M., and Harris, E.W. (1981). Synapse replacement in the nervous system of adult vertebrates. Physiol. Rev., 61: 684–784.PubMedGoogle Scholar
  13. Das, G.D. (1983). Neural Transplantation in the spinal cord of the adult mammals. In C.C. Kao, R.P. Bunge, and P.J. Reier (Eds), Spinal Cord Reconstruction, Raven Press, New York. pp. 367–397.Google Scholar
  14. Daszuta, A., Marocco C., and Bosler, O. (1991). Serotonin reinnervation of the suprachiasmatic nucleus by intra-hypothalamic fetal raphe transplants, with special reference to possible influences of the target. Fur: J. Neurosci., 3: 1330–1337.CrossRefGoogle Scholar
  15. Fisher, L.J., and Gage, F.H. (1993). Grafting in the mammalian central nervous system. Physiol. Rev., 73: 583–616.PubMedGoogle Scholar
  16. Forssberg, H., and Grillner, S. (1973). The locomotion of the acute spinal cat injected with clonidine i.v., Brain Res., 50: 184–186.PubMedCrossRefGoogle Scholar
  17. Foster, G.A., Schultzberg, M., Gage, F.H., Björklund, A., Hökfelt, T., Names, H., Cuello, A.C., Verhofstad, A.A.J., and Visser, T.J. (1985). Transmitter expression and morphological development of embryonic medullary and mesencephalic raphe neurons after transplantation to the adult rat central nervous system. L Grafts to the spinal cord. Exp. Bruin. Res., 60: 427–444.Google Scholar
  18. Freed, W.J. (1993). Neural transplantation: Prospects for clinical use. Cell Transplantation, 2: 13–31.Google Scholar
  19. Fritschy, J.M., Lyons. W.E., Mullen, C.A., Kosofsky, B.E., Molliver, M.E., and Grzanna, R. (1987). Distribution ofGoogle Scholar
  20. locus coeruleus axons in the rat spinal cord: a combined anterograde transport and immunohistochemica study. Brain Res.,437: 176–180.Google Scholar
  21. Giron, L.T., Maccann, S.A., and Crist-Orlando, S.G. (1985). Pharmacological characterization and regional distribution of alpha-noradrenergic binding sites of rat spinal cord. Ew: J. Pharmacol., 115: 285–290.CrossRefGoogle Scholar
  22. Goldberger, M.E., Murray, M., and Tessler, A. (1993a). Sprouting and regeneration in the spinal cord–Their roles in recovery of function after spinal injury. In A. Gorio (Ed), Neuroregeneration. Raven Press, New York. pp. 241–264.Google Scholar
  23. Goldberger, M.E., Murray, M., and Tessler, A. (1993b). Grafts and functional recuperation. Rest. Neural. Neuro-sci., 5: 69–75.Google Scholar
  24. Hankin, M., and Lund, R. (1991). How do retinal axons find their targets in the developing brain? Trends Neuro-sci., 14: 224–228.CrossRefGoogle Scholar
  25. Jones, D.J., Kendall, D.E., and Enna, S.J. (1982). Adrenergic receptors in rat spinal cord. Neuropharmacologv, 21: 191–195.CrossRefGoogle Scholar
  26. König, N., Rajaofetra, N., Sandillon, F., Drian, M.J., Fuentes, C., Favier, F., and Privat, A. (1989). Serotonin-expressing cells from different microregions of the embryonic rat rhombencephalon: Behaviour in cell culture and in transplantation to the adult spinal cord. In F. Gage, A. Privat, and Y. Christen (Eds), Neuronal grafting and Alzheimer’s disease. Springer-Verlag, Berlin. pp. 150–166.CrossRefGoogle Scholar
  27. König, N., Wilkie, M.B., and Lauder, J. (1988). Tyrosine hydroxylase and serotonin containing cells in embryonicrat rhombencephalon: a whole-mount immunocytochemical study. J. Neurosci. Res., 20: 212–223.PubMedCrossRefGoogle Scholar
  28. Kunkel-Bagden, E., and Bregman, B.S. (1990). Spinal cord transplants enhance the recovery of locomotor function after spinal cord injury at birth. Exp. Brain Res., 81: 25–34.PubMedCrossRefGoogle Scholar
  29. Mas, M., Zahradnik, M.A., Martino, V., and Davidson, J.M. (1985). Stimulation of spinal serotonergic receptors facilitates seminal emission and suppresses penile erectile reflexes. Brain Res., 342: 128–134.PubMedCrossRefGoogle Scholar
  30. Mason, S.T., and Fibiger, H.C. (1979). Physiological function of descending noradrenaline projections to the spinal cord: Rôle in post decapitation convulsions. Eut: J. Pharmacol., 57: 29–34.CrossRefGoogle Scholar
  31. Molander, C., Xu, Q., and Grant, G. (1984). The cytoarchitectonic organitation of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord. J. Comp. Neural., 230: 133–141.CrossRefGoogle Scholar
  32. Molander, C., Xu, Q., Rivermelian, C., and Grant, G. (1989). The cytoarchitectonic organization of the spinal cord in the rat. II. The cervical and upper thoracic]cord. J. Comp. Neurol., 289: 375–385.PubMedCrossRefGoogle Scholar
  33. Moorman, S.J., Whalen, L.R., and Nornes, H.O. (1990). A neurotransmitter specific functional recovery mediated by fetal implants in the lesioned spinal cord of the rat. Brain Res., 508: 194–198.PubMedCrossRefGoogle Scholar
  34. Mouchet, P., Manier, M., and Feuerstein, C. (1992). Immunohistochemical study of the catecholaminergic innervation of the spinal cord of the rat using specific antibodies against dopamine and noradrenaline. J. Chen. Neuroanat., 5: 427–440.CrossRefGoogle Scholar
  35. Nieto-Sampedro, M., Kesslak, J.P., Gibbs, R., and Cotman, C.W. (1987). Effects of conditionng lesions on transplant survival, connectivity, and function. In E.C. Azmitia, and A. Björklund (Eds), Cell and Tissue Trans-plantation into the Adult Brain. The New York Academy of Sciences, New York. pp. 108–119.Google Scholar
  36. Nishino, H. (1993). Intracerebral grafting of catecholamine producing cells and reconstruction of disturbed brain function. Neurosci. Res., 16: 157–172.PubMedCrossRefGoogle Scholar
  37. Nornes, H., Björklund, A., and Stenevi, U. (1983). Reinnervation of the denervated adult spinal cord of rats by intraspinal transplant of embryonic brain stem neurons. Cell Tissue Res., 230: 15–35.PubMedCrossRefGoogle Scholar
  38. Nomes, H., Björklund, A., and Stenevi, U. (1984). Transplant strategies in spinal cord regeneration. In J.R. Sladek, and D.M. Gash (Eds), Neural Transplants: Development and Function, Plenum Press, New York. pp. 407–421.Google Scholar
  39. Nothias, F., Horvat, J.C., Mira, J.C., Pecot-Dechavassine, M., and Peschanski, M. (1990). Double step neural transplants to replace degenerated motoneurons. Neural Transplantation: From molecular basis to clinical applications. Prog. Brain Res., 82: 239–246.PubMedCrossRefGoogle Scholar
  40. Nothias, F., and Peschanski, M. (1990). Homotypic fetal transplants into an experimental model of spinal cord neurodegeneration. J. Comp. Neural., 301: 520–534.CrossRefGoogle Scholar
  41. Nygren, L.G., Olson, L., and Seiger, A. (1977). Monoaminergic reinnervation of the transected spinal cord by homologous fetal brain grafts. Brain Res., 129: 225–235.CrossRefGoogle Scholar
  42. Onifer, S.M., Whittemore, S.R., and Holets, V.R. (1993). Variable morphological differentiation ofa raphé-derived neuronal cell line following transplantation into the adult rat CNS. Exp. Neurol. 122: 130–142.PubMedCrossRefGoogle Scholar
  43. Peretti-Renucci, R., Feuerstein, C., Manier, M., Lorimier, P., Savasta, M., Thibault, J., Mons, N. and Geffard, M. (1991). Quantitative image analysis with densitometry for immunohistochemistry and autoradiography of receptor binding sites. J. Neurosci. Res., 28: 583–600.PubMedCrossRefGoogle Scholar
  44. Privat, A., Mansour, H., and Geffard, M. (1988). Transplantation of fetal serotonin neurons into the transected spinal cord of adult rats: morphological development and functional influence. In D.M. Gash, and J.R. Sladek (Eds), Transplantation into the Mammalian Central Nervous System, Progress in Brain Research, Vol. 78. Elsevier, Amsterdam, pp. 155–166.Google Scholar
  45. Privat, A., Mansour, H., Pavy, A., Geffard, M. and Sandillon, F. (1986). Transplantation of dissociated foetal serotonin neurons into the transected spinal cord of adult rats, Neurosci. Lett., 66: 61–66.PubMedCrossRefGoogle Scholar
  46. Privat, A., Mansour, H., Rajaofetra, N., and Geffard, M. (1989). Intraspinal transplant of serotonergic neurons in the adult rat. Brain Res. Bull. 22: 123–129.PubMedCrossRefGoogle Scholar
  47. Rajaofetra, N., Kachidian, P., Marlier, L., Poulat, P., Konig, N., Geffard. M., and Privat, A. (1991). Electronmicroscopic detection of the axonal coexistence of serotonin and substance-P in BI-B2 raphe cells transplanted into the transected spinal cord of adult rats. Brain Res., 542: 159–162.Google Scholar
  48. Rajaofetra, N., König, N., Poulat, P., Marlier, L., Sandillon, F., Drian, M.J., Geffard, M., and Privat, A. (1992a). Fate of Bl-B2 and B3 rhombencephalic cells transplanted into the transected spinal cord of adult rats: Light and electron microscopic studies. Exp. Neural., 117: 59–70.CrossRefGoogle Scholar
  49. Rajaofetra, N., Ridet, J.L., Poulat, P., Manlier, L., Sandillon, F., Geffard, M., and Privat, A. (1992b). Immunocytochemical mapping of noradrenergic projections to the rat spinal cord with an antiserum against noradrenaline. J. Neurocytol., 21: 481–494.PubMedCrossRefGoogle Scholar
  50. Ramón y Cajal, S. (1892). La rétine de vertebrés. In Lu Cellule, Vol IX,.pp. 119–158.Google Scholar
  51. Rawlow, A., and Gorka, Z. (1986). Involvement of post-synaptic al and a2-adrenoceptors in the flexor reflex activity in the spinal rats. J. Neural Trans., 66: 93–105.CrossRefGoogle Scholar
  52. Reier, P.J., Bregman, B.S., Wujek, J.R., and Tessler, A. (1986). Intraspinal transplantation of fetal spinal cord tissue: An approach toward functional repair of the injured spinal cord. In M.E. Goldberger, A. Gorio, and M. Murray (Eds), Development und Plasticity of the Mammalian Spinal Cord, Fidia Research Series, vol. III, Liviana Press, Padova. pp. 251–269.Google Scholar
  53. Reier P.J., Houle, J.D., Jakeman, L., Winialski, D., and Tessler, A. (1988). Transplantation of fetal spinal cord tissue into acute and chronic hemisection and contusion lesions of the adult rat spinal cord. In D.M. Gash, and J.R. Sladek. Jr. (Eds), Transplantation in the Mammalian CNS, Elsevier, Amsterdam. pp. I73–179.Google Scholar
  54. Reier, P.J., Stokes, B.T., Thompson, F.J., and Anderson, D.K. (1992). Fetal cell grafts into resection and contusion/compression injuries of the rat and cat spinal cord. Exp. Neurol., 115: 177–188.PubMedCrossRefGoogle Scholar
  55. Rossignol S., Barbeau, H., and Julien, C. (1986). Locomotion of the adult chronic spinal cat and its modification by monoaminergic agonists and antagonists. In M.E. Goldberger, A. Gorio, and M. Murray (Eds), Development and Plasticity of the Mammalian Spinal Cord, Fidia Research Series, vol III, Liviana Press, Padova. pp. 323–345.Google Scholar
  56. Roudet, C., Savasta M., and Feuerstein, C. (1993). Normal distribution of alpha-l-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: A quantitative autoradiographic study. J. Neuro-sci. Res., 34: 44–53.CrossRefGoogle Scholar
  57. Roudet, C., Mouchet, M., Feuerstein, C., and Savasta M. (1994). Normal distribution of of alpha-2 adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study. J. Neurosci. Res., 39: 319–329.PubMedCrossRefGoogle Scholar
  58. Shi, H., Lewis, D.I., and Coote, J.H. (1988). Effects of activating spinal a-adrenoceptors on sypathetic nerve activity in the rat. J. Autan. Nerv. Syst., 23: 69–78.CrossRefGoogle Scholar
  59. Simmons, R.M., and Jones, D.J. (1988). Binding of [3H]-Prazosin and [3H]-p-aminoclonidine to a-adrenoceptors in rat spinal cord. Brain Res., 23: 338–343.CrossRefGoogle Scholar
  60. Stokes, B. T., and Reier, P.J. (1992). Fetal grafts alter chronic behavioral outcome after contusion damage to the adult rat spinal cord. Exp. Neural., 116: 1–12.CrossRefGoogle Scholar
  61. Tanabe, M., Ono, H., and Fukuda, H. (1990). Spinal alpha 1- and alpha 2-adrenoceptors mediate facilitation and inhibition of spinal motor transmission respectively. Jpn. J. Pharmacol., 54: 69–77.PubMedCrossRefGoogle Scholar
  62. Tessier-Lavigne, M., Placzek, M., Lumsden, A.G.S., Dodd, J., and Jessell, T.M. (1988). Chemotropic guidance of developing axons in the mammalian central nervous system. Nature, 336: 775–778.PubMedCrossRefGoogle Scholar
  63. Tessier-Lavigne, M., and Placzek, M. (1991). Target attraction: are developing axons guided by chemotropism? Trends Neurosci., 14: 303–310.PubMedCrossRefGoogle Scholar
  64. Tessier-Lavigne M., and Goodman C.S. (1996). The molecular biology of axon guidance. Science, 274: 1123–1133.PubMedCrossRefGoogle Scholar
  65. Tessler, A. (1991). Intraspinal Transplants. Ann. Neurol., 29: 115–123.PubMedCrossRefGoogle Scholar
  66. Tessler, A., Goldberger, M.E., Himes, B.T., Howland, D.R., Itoh, Y., and Pinter, M.J. (1992). Transplant mediated mechanisms of locomotor recovery. Rest. Neurol. Neurosci., 5: 64–65.Google Scholar
  67. Unnerstall, J.R., Kopajtic, T.A., and Kuhar, M.J. (1984). Distribution of a2 agonist binding sites in the rat and human central nervous system: Analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents, Brain Res. Rev., 7: 69–101.CrossRefGoogle Scholar
  68. Vuillet, J., Moukhles, H., Nieoullon, A., and Daszuta, A. (1994). Ultrastructural analysis of graft-to-host connections, with special reference to dopamine-neuropeptide Y interactions in the rat striatum, after transplantation of fetal mesencephalon cells. Exp. Brain Res., 98: 84–96.PubMedCrossRefGoogle Scholar
  69. Westlund, K.N., Bowker, R.M., Ziegler, M.G., and Coulter, J.D. (1982). Descending noradrenergic projections and their spinal terminations. In H.G.J.M. Kuypers, and G.F. Martin (Eds), Descending Pathways to the Spinal Cord, Progress in Brain Research, Vol. 57, Elsevier, Amsterdam. 219–238.Google Scholar
  70. Westlund, K.N., Bowker, R.M., Ziegler, M.G., and Coulter, J.D. (1983). Noradrenergic projections to the spinal cord of the rat. Brain Res., 263: 15–31.PubMedCrossRefGoogle Scholar
  71. Wictorin, K., Simerly, R.B., lsacson, O., Swanson, L.W., and Björklund, A. (1992). Connectivity of striatal grafts implanted into the ibotenic acid lesioned striatum. III. Efferent projecting graft neurons and their relation to host afferents within the graft. Neuroscience, 30: 313–330.CrossRefGoogle Scholar
  72. Xu, Z.C., Wilson, C.J., and Emson, P.C. (1992). Morphology of intracellularly stained spiny neurons in rat striatal grafts. Neuroscience, 48: 95–110.PubMedCrossRefGoogle Scholar
  73. Yakovleff, A., Roby-Brami, A., Guezard, B., Mansour, H., Bussel, B., and Privat, A. (1989). Locomotion in rats transplanted with noradrenergic neurons. Brain Res. Bull., 22: 115–121.PubMedCrossRefGoogle Scholar
  74. Yakovleff, A., Cabelguen J.M., Orsal, D., Giménez y Ribotta, M., Rajaofetra, N., Drian M.J., Bussel, B., and Privat A. (1995). Fictive motor activities in adult chronic spinal rats transplanted with embryonic brainstem neurons. Exp. Brain Res., 106: 69–78. 136 M. Giménez y Ribotta et al.Google Scholar
  75. Young, W.S., and Kunhar, M.J. (1980). Noradrenergic al and a2 receptors: light microscopic autoradiographie localization. Prot. Natl. Acad. Sci. U.S.A. 77: 1696 1700.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Minerva Giménez y Ribotta
    • 1
  • Christelle Roudet
    • 1
  • Alain Privat
    • 1
  1. 1.INSERM U. 336, Developpement Plasticité et Vieillissement du Système NerveuxUniversité Montpellier II.MontpellierFrance

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