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Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat central nervous system

III. Grafts to the striatum

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Summary

Implants have been made of dissociated embryonic mesencephalic or medullary raphé cells into the adult rat striatum, previously depleted of its 5HT innervation. The transmitter complement and fibre outgrowth of the grafted neurones were analysed immunocytochemically. Serotonin-containing cells were found in both types of transplant, and the proportionate survival of the potential number of implanted 5HT cells was similar for each type of graft. However, these proportions were both greater than that described previously in transplants of mesencephalic raphé cells to the spinal cord. In addition, the proportionate survival of medullary substance P neurones grafted to the striatum was greater than that of medullary 5HT cells implanted in the same region. The transmitter complement of the medullary neurones was largely unaltered after transplantation. However, the mesencephalic grafts contained neurones storing 5HT- and/or substance P-, or TRH-like immunoreactivity. The 5HT/substance P and TRH neurones have so far not been encountered in the mesencephalon in situ using the present immunohistochemical methodology. Invasion of the host striatum by 5HT processes from the transplanted mesencephalic cells was extensive. Fibres from medullary raphé neurones, however, were restricted principally to within the graft itself. It is concluded that there may exist in the adult rat striatum a set of trophic factors for 5HT and substance P neurones different from those found in other regions of the central nervous system, such as spinal cord. Moreover, trophic agents in the host striatum appear to operate differentially on mesencephalic and medullary raphé 5HT neurones to regulate their axonal outgrowth. Lastly, the neurotransmitter phenotypic expression of the embryonic mesencephalic raphé cells may be susceptible to influences from the host environment.

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References

  • Adler R, Manthorpe M, Skaper S, Varon S (1981) Polyornithine-bound neurite-promoting factors (PNPFs): culture sources and responsive neurons. Brain Res 206: 129–144

    Google Scholar 

  • Anderson KJ, Gibbs RB, Salvaterra PM, Cotman CW (1986) Ultrastructural characterization of identified cholinergic neurons transplanted to the hippocampal formation of the rat. J Comp Neurol 249: 279–292

    Google Scholar 

  • Baron von Evercooren A, Kleinman HK, Ohno S, Marangos P, Schwartz JP, Dubois-Dalcq ME (1981) Nerve growth factor, laminin and fibronectin promote neurite outgrowth in human fetal sensory ganglia cultures. J Neurosci Res 8: 179–194

    Google Scholar 

  • Baumgarten HG, Björklund A, Lachenmayer L, Fensch A, Rosengren E (1974) De- and regeneration of the bulbospinal serotonin neurons in the rat following 5,6- or 5,7-dihydroxytryptamine treatment. Cell Tiss Res 152: 271–281

    Google Scholar 

  • Björklund A, Skagerberg G (1982) Descending monoaminergic projections to the spinal cord. In: Björklund A, Sjölund B (eds) Brain Stem control of spinal cord mechanisms. Elsevier Biomedical Press, Amsterdam, pp 55–88

    Google Scholar 

  • Björklund A, Stenevi U (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 177: 555–560

    Google Scholar 

  • Björklund A, Gage FH, Schmidt RH, Stenevi U, Dunnett SB (1983a) Recovery of choline acetyltransferase activity and acetylcholine synthesis in the denervated hippocampus reinnervated by septal suspension implants. Acta Physiol Scand Suppl 522: 59–66

    Google Scholar 

  • Björklund A, Stenevi U, Schmidt RH, Dunnett SB, Gage FH (1983b) Intracerebral grafting of neuronal cell suspensions. 1. Introduction and general methods of preparation. Acta Physiol Scand Suppl 522: 1–7

    Google Scholar 

  • Björklund A, Stenevi U, Schmidt RH, Dunnett SB, Gage FH (1983c) Survival and growth of nigral cell suspensions implanted in different brain sites. Acta Physiol Scand Suppl 522: 9–18

    Google Scholar 

  • Björklund H, Hökfelt T, Goldstein M, Terenius L, Olson L (1985) Appearance of the noradrenergic markers tyrosine hydroxylase and neuropeptide Y in cholinergic nerves of the iris following sympathectomy. J Neurosci 5: 1633–1643

    Google Scholar 

  • Blackburn TP, Foster GA, Heapy CG, Kemp JD (1980) Unilateral 5,7-dihydroxytryptamine lesions of the dorsal raphe nucleus (DRN) and rat rotational behaviour. Eur J Pharmacol 67: 427–438

    Google Scholar 

  • Bowker RM, Westlund KN, Coulter JD (1981) Origins of serotonergic projections to the spinal cord in rat: an immunocytochemical-retrograde transport study. Brain Res 226: 187–199

    Google Scholar 

  • Bowker RM, Westlund KN, Sullivan MC, Wilber JF, Coulter JD (1983) Descending serotonergic, peptidergic and cholinergic pathways from the raphe nuclei: a multiple transmitter complex. Brain Res 288: 33–48

    Google Scholar 

  • Bregman BS, Reier PJ (1986) Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death. J Comp Neurol 244: 86–95

    Google Scholar 

  • Brundin P, Isaacson O, Björklund A (1985) Monitoring of cell viability in suspensions of embryonic CNS tissue and its use as a criterion for intracerebral graft survival. Brain Res 331: 251–259

    Google Scholar 

  • Buzsaki G, Gage FH, Czof J, Björklund A (1987) Restoration of rhythmic slow activity (Θ) in the subcortically denervated hippocampus by fetal CNS transplants. Brain Res 400: 334–347

    Google Scholar 

  • Clarke D, Gage FH, Björklund A (1986) Formation of cholinergic synapses by intrahippocampal septal grafts as revealed by choline acetyltransferase immunohistochemistry. Brain Res 369: 151–162

    Google Scholar 

  • Cuello AC, Galfré G, Milstein C (1970) Detection of substance P in the central nervous system by a monoclonal antibody. Proc Natl Acad Sci USA 6: 3532–3536

    Google Scholar 

  • Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurones. Acta Physiol Scand Suppl 232: 1–55

    Google Scholar 

  • Dahlström A, Fuxe K (1965) Evidence for the existence of monoamine-containing neurons in the central nervous system. II. Experimentally induced changes in the intra-neuronal amine levels. Acta Physiol Scand Suppl 247: 1–36

    Google Scholar 

  • Descarries L, Beaudet A, Watkins JC, Garcis S (1979) The serotonin neurons in the nucleus raphe dorsalis of adult rat. Anat Rec 193: 520

    Google Scholar 

  • Drucker-Colin R, Aguilar-Roblero R, Garcia-Hernandez F, Fernandez-Cancino F, Bermudez Rattoni F (1984) Fetal suprachiasmatic nucleus transplants: diurnal rhythm recovery of lesioned rats. Brain Res 311: 353–357

    Google Scholar 

  • Dunn EH (1917) Primary and secondary findings in a series of attempts to transplant cerebral cortex in the albino rat. J Comp Neurol 27: 565–572

    Google Scholar 

  • Dunnett SB, Björklund A, Stenevi U, Iversen SD (1981) Grafts of embryonic substantia nigra reinnervating the ventrolateral striatum ameliorate sensorimotor impairments and akinesia in rats with 6-OHDA lesions of the nigrostriatal pathway. Brain Res 229: 209–217

    Google Scholar 

  • Dunnett SB, Whishaw IQ, Bunch ST, Fine A (1986) Acetylcholine-rich neuronal grafts in the forebrain of rats: effects of environmental enrichment, neonatal noradrenaline depletion, host transplantation site and regional source of embryonic donor cells on graft size and acetylcholinesterase-positive fibre outgrowth. Brain Res 378: 357–373

    Google Scholar 

  • Foster GA, Schultzberg M, Björklund A, Gage FH, Hökfelt T (1985a) Fate of embryonic mesencephalic and medullary raphé neurones transplanted to the striatum, hippocampus and spinal cord of the adult rat: analysis of 5-hydroxytryptamine-, substance P- and thyrotropin releasing hormoneimmunoreactive cells. In: Björklund A, Stenevi U (eds) Transplantation in the mammalian CNS. Elsevier Biomedical Press, Amsterdam, pp 179–189

    Google Scholar 

  • Foster GA, Schultzberg M, Gage FH, Björklund A, Hökfelt T, Nornes H, Cuello AC, Verhofstad AAJ, Visser TJ (1985b) Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat nervous system. I. Grafts to the spinal cord. Exp Brain Res 60: 427–444

    Google Scholar 

  • Foster GA, Schultzberg M, Gage FH, Björklund A, Hökfelt T, Cuello AC, Verhofstad AAJ, Visser TJ, Emson PC (1988) Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat central nervous system. II. Grafts to the hippocampus. Exp Brain Res 70: 225–241

    Google Scholar 

  • Freed WJ, Perlow MJ, Karoum F, Seiger Å, Olson L, Hoffer BJ, Wyatt RJ (1980) Restoration of dopaminergic function by grafting of fetal substantia nigra to the caudate nucleus: longterm behavioral, biochemical and histochemical studies. Ann Neurol 8: 510–526

    Google Scholar 

  • Freund TF, Bolam JP, Björklund A, Stenevi U, Powell JF, Smith AD (1985) Efferent synaptic connections of grafted dopaminergic neurones reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study. J Neurosci 5: 603–616

    Google Scholar 

  • Fuxe K, Jonsson G (1974) Further mapping of central 5-hydroxytryptamine neurons: studies with neurotoxic dihydrotryptamines. Adv Biochem Psychopharm, Vol 10, Raven Press, New York, pp 1–12

    Google Scholar 

  • Gage FH, Björklund A (1986) Enhanced graft survival in the hippocampus following selective denervation. Neuroscience 17: 89–98

    Google Scholar 

  • Gage FH, Björklund A, Stenevi U (1984a) Denervation releases a neuronal survival factor in adult rat hippocampus. Nature (Lond) 308: 637–639

    Google Scholar 

  • Gage FH, Björklund A, Stenevi U, Dunnett SB, Kelly PAT (1984b) Intrahippocampal septal grafts ameliorate learning impairment in aged rats. Science 225: 533–536

    Google Scholar 

  • Gähwiler BH, Hefti F (1984) Guidance of acetylcholinesterase-containing fibres by target tissue in co-cultured brain slices. Neuroscience 13: 681–689

    Google Scholar 

  • Gash DM, Sladek JR Jr, Sladek CD (1980) Functional development of grafted vasopressin neurons. Science 210: 1367–1369

    Google Scholar 

  • Hamburger V, Levi-Montalcini R (1949) Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J Exp Zool 111: 457–501

    Google Scholar 

  • Haun F, Cunningham TJ (1984) Cortical transplants reveal CNS trophic interactions in situ. Dev Brain Res 15: 290–294

    Google Scholar 

  • Haydon PG, McCobb DP, Kater SB (1982) Serotonin selectively inhibits growth cone motility and synaptogenesis of specific identified neurons. Science 226: 561–564

    Google Scholar 

  • Johansson O, Hökfelt T, Pernow B, Jeffcoate SL, White N, Steinbusch HWM, Verhofstad AAJ, Emson PC, Spindel E (1981) Immunohistochemical support for three putative transmitters in one neuron: coexistence of 5-hydroxytryptamine-, substance P- and thyrotropin releasing hormone-like immunoreactivity in medullary neurones projecting to the-spinal cord. Neuroscience 6: 1857–1881

    Google Scholar 

  • Johnson DG, De C Nogueira Araujo GM (1981) A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Meth 43: 349

    Article  CAS  PubMed  Google Scholar 

  • Kessler JA, Black IB (1982) Regulation of substance P in adult rat sympathetic ganglia. Brain Res 234: 182–187

    Google Scholar 

  • Königsmark BW (1970) Methods for the counting of neurons. In: Nauta WH, Ebbeson SOE (eds) Contemporary research methods in neuroanatomy. Springer, New York, pp 315–321

    Google Scholar 

  • Krieger DT, Perlow MJ, Gibson MJ, Davies TF, Zimmerman EA, Ferin M, Charlton HM (1982) Brain grafts reverse hypogonadism or gonadotropin-releasing hormone deficiency. Nature (Lond) 298: 468–471

    Google Scholar 

  • Labbe R, Firl A, Mufson EJ, Stein DG (1983) Fetal brain transplants: reduction of cognitive deficits in rats with frontal cortex lesions. Science 221: 470–472

    Google Scholar 

  • Le Douarin NM, Teillet MA, Ziller C, Smith J (1978) Adrenergic differentiation of cells of the cholinergic ciliary and Remak ganglia in avian embryos after in vivo transplantation. Proc Natl Acad Sci USA 75: 2030–2034

    Google Scholar 

  • Levi-Montalcini R, Hamburger V (1951) Selective growth-stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 123: 233–287

    Google Scholar 

  • Longo FM, Hayman EG, Davis GE, Ruoslahti E, Engvall E, Manthorpe M, Varon S (1984) Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers. Brain Res 309: 105–117

    Google Scholar 

  • Lewis ER, Cotman CW (1983) Neurotransmitter characteristics of brain grafts: striatal and septal tissues form the same laminated input to the hippocampus. Neuroscience 8: 57–66

    Google Scholar 

  • Ljungdahl A, Hökfelt T, Nilsson G (1978) Distribution of substance P-like immunoreactivity in the central nervous system of the rat. I. Cell bodies and nerve terminals. Neuroscience 3: 861–943

    Article  CAS  PubMed  Google Scholar 

  • Lorez HP, Saner A, Richards JG (1978) Evidence against a neurotoxic action of halogenated amphetamines on serotoninergic B9 cells. A morphometric fluorescence histochemical study. Brain Res 146: 1889–1894

    Google Scholar 

  • Mahalik TJ, Finger TE, Strömberg I, Olson L (1985) Substantia nigra transplants into denervated striatum of the rat: ultrastructure of graft and host interconnections. J Comp Neurol 240: 60–70

    Google Scholar 

  • Markey KA, Kondo S, Shenkman I, Goldstein M (1980) Purification and characterization of tyrosine hydroxylase from a clonal phaeochromocytoma cell line. Mol Pharamcol 17: 79–85

    Google Scholar 

  • Matthews MA, West LC, Riccio RV (1982) An ultrastructural analysis of the development of foetal rat retina transplanted to the occipital cortex, a site lacking appropriate target neurons for optic fibers. J Neurocytol 11: 533–557

    Google Scholar 

  • McLoon SC, Lund RD (1984) Loss of ganglion cells in fetal retina transplanted to rat cortex. Developmental Brain Res 12: 131–135

    Google Scholar 

  • Nygren L-G, Olson L (1977) Intracisternal neurotoxins and monoamine neurons innervating the spinal cord: acute and chronic effects on cell and axon counts and nerve terminal densities. Histochemistry 52: 281–306

    Google Scholar 

  • Okado N, Oppenheim RW (1984) Cell death of motoneurons in the chick embryo spinal cord. IX. The loss of motoneurons following removal of afferent inputs. J Neurosci 4: 1639–1652

    Google Scholar 

  • Olson L, Seiger Å (1972) Early prenatal ontogeny of central monoamine neurones in the rat: fluorescence histochemical observations. Z Anat Entwickl-Gesch 137: 301–316

    Google Scholar 

  • Patterson PH, Chun LLY (1977) The induction of acetylcholine synthesis in the primary cultures of dissociated rat sympathetic neurones. I. Effects of conditioned medium. Dev Biol 56: 263–280

    Google Scholar 

  • Pease PC (1962) Buffered formaldehyde as a killing agent and primary fixative for electron microscopy. Anat Res 142: 342

    Google Scholar 

  • Perlow MJ, Freed WJ, Hoffer BJ, Seiger Å, Olson L, Wyatt RJ (1979) Brain grafts reduce abnormalities produced by destruction of nigrostriatal dopamine system. Science 204: 643–647

    Google Scholar 

  • Schmidt RH, Ingvar M, Lindvall O, Stenevi U, Björklund A (1982) Functional activity of substantia niga grafts reinnervating the striatum: neurotransmitter metabolism and 14[C]-2-deoxy-D-glucose autoradiography. J Neurochem 38: 737–748

    Google Scholar 

  • Schultzberg M, Dunnett SB, Björklund A, Stenevi U, Hökfelt T, Dockray GJ, Goldstein M (1984) Dopamine and cholecystokinin immunoreactive neurones in mesencephalic grafts reinnervating the neostriatum: evidence for selective growth regulation. Neuroscience 12: 17–32

    Google Scholar 

  • Segal M, Björklund A, Gage FH (1985) Intracellular analysis of cholinergic synapses between grafted septal nuclei and host hippocampal pyramidal neurones. In: Björklund A, Stenevi U (eds) Neural grafting in the mammalian CNS, Elsevier Biomedical Press, Amsterdam, pp 389–399

    Google Scholar 

  • Sofroniew MV, Isaacson O, Björklund A (1986) Cortical grafts prevent atrophy of cholinergic basal nucleus neurons induced by excitotoxic cortical damage. Brain Res 378: 409–415

    Google Scholar 

  • Steinbusch HWM, Verhofstad AAJ, Joosten HWJ (1978) Localization of serotonin in the central nervous system by immunohistochemistry. Description of specific and sensitive technique and some applications. Neuroscience 3: 811–819

    Google Scholar 

  • Tohyama M, Sakai K, Touret M, Salvert D, Jouvet M (1979) Spinal projections from the lower brain stem in the cat as demonstrated by the horse radish peroxidase technique. II. Projections from the dorsolateral pontine tegmentum and raphe nuclei. Brain Res 176: 215–231

    Google Scholar 

  • Tramu G, Pillez A, Leonardelli J (1978) An efficient method of antibody elution for the successive of simultaneous location of two antigens by immunocytochemistry. J Histochem Cytochem 26: 322–324

    Google Scholar 

  • Tsuruo Y, Hökfelt T, Visser T (1987) Thyrotropin releasing hormone (TRH) immunoreactive cell groups in the rat central nervous system. Exp Brain Res 68: 213–217

    Google Scholar 

  • Verhofstad AAJ, Steinbusch HWM, Joosten HWJ, Penke B, Varga J, Goldstein M (1983) Immunocytochemical localization of noradrenaline, adrenaline and serotonin. In: Polak JM, Van Noorden S (eds) Immunocytochemistry. Practical applications in pathology and biology. Wright PSG, Bristol, pp 143–168

    Google Scholar 

  • Visser TJ, Klootwijk W, Doctor R, Henneman G (1977) A different approach to the radioimmunoassay of thyrotropin releasing hormone. In: Radioimmunoassay and related procedures in medicine. National Atomic Energy Agency, Vienna, pp 469–477

    Google Scholar 

  • Zamboni L, de Martino C (1967) Buffered picric-acid formaldehyde: a new rapid fixative for electron-microscopy. J Cell Biol 35: 148A

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  1. M. Schultzberg

    Present address: Department of Pathology, Neuropathol. Div., Huddinge University Hospital, S-14186, Huddinge, Sweden

Authors and Affiliations

  1. Dept. of Histology, Karolinska Inst., S-10401, Stockholm, Sweden

    G. A. Foster, M. Schultzberg & T. Hökfelt

  2. Dept. of Neurosciences, Univ. of California, 92093, La Jolla, CA, USA

    F. H. Gage

  3. Dept. of Histology, Univ., S-22362, Lund, Sweden

    F. H. Gage & A. Björklund

  4. Dept. of Pharmacology and Therapeutics, McGill Univ., H3G 1V6, Montreal, Canada

    A. C. Cuello

  5. Dept. of Anatomy and Embryology, Univ. of Nijmegen, NL-6525, Nijmegen, The Netherlands

    A. A. J. Verhofstad

  6. Dept. of Internal Medicine and Clinical Endocrinology, Erasmus Univ. Medical School, NL-3000, DR Rotterdam, The Netherlands

    T. J. Visser

  7. Dept. of Neuroendocrinology, MRC Group, Inst. of Animal Physiology, CB2 4AT, Babraham, Cambridge, UK

    P. C. Emson

  8. Department of Physiology, University College, PO Box 78, CF1 1XL, Cardiff, UK

    G. A. Foster

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Foster, G.A., Schultzberg, M., Gage, F.H. et al. Transmitter expression and morphological development of embryonic medullary and mesencephalic raphé neurones after transplantation to the adult rat central nervous system. Exp Brain Res 70, 242–255 (1988). https://doi.org/10.1007/BF00248350

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