Skip to main content
SpringerLink
Log in

A Neurotrophic Factor — SNTF — for Serotonergic Neurons

  • Chapter
Serotonin: Molecular Biology, Receptors and Functional Effects

Summary

We have found that the 5-HT target tissue of denervated adult rat brain contains high levels of a serotonergic neurons related-trophic factor(s) [SNTF]. Specific denervation of 5-HT fibers from the hippocampus [by 5,7-dihydroxytryptamine injection in the afferent pathway] induces 5-HT homotypic collateral sprouting in a month. The 5-HT-denervated hippocampus was shown to be a rich environment for the growth of grafted fetal 5-HT neurons. Grafted fetal 5-HT neurons exhibited higher 5-HT levels and 5-HT synaptosomal high-affinity uptake, more dense fibers and larger cell bodies in the 5-HT-denervated hippocampus than in normal hippocampus. Extracts [hypotonic solution in high-speed supernatant fraction] obtained from the denervated hippocampus were found to be trophic in vitro and in vivo. Extracts placed in raphe cell culture [rich in 5-HT neurons] increased the 5-HT high-affinity uptake. Extracts when added to grafted 5-HT neurons increased the 5-HT content of fetal 5-HT neurons in the normal hippocampus. The grafted 5-HT neurons and trophic extracts were also tested in the cerebellum, a brain region with sparse 5-HT innervation. We found that grafted 5-HT neurons seldom survived in this brain region. The denervated hippocampal extracts greatly increased the survival rate of the grafted 5-HT neurons, and significantly increased the density of the fibers in the cerebellum. These observations indicate that brain derived SNTF is trophic to 5-HT neurons at three levels — survival, neurite extension and transmitter maturation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Abercrombie, M. (1946). Estimation of nuclear population from microtome sections. Anat. Rec. 94: 239–247.

    Article  Google Scholar 

  • Adler, R., Landa, K. B., Manthrope, M., and Varon, S. (1979). Cholinergic neuronotrophic factors. II. Selective intraocular distribution of soluble trophic activity for ciliary ganglionic neurons. Science 204: 1434–1436.

    Article  Google Scholar 

  • Auerbach, S., Zhou, F. C., Jacobs, B. L., and Azmitia, E. C. (1985). Serotonin turnover in raphe neurons transplanted into rat hippocampus. Neurosci. Lett. 61: 147–152.

    Google Scholar 

  • Azmitia, E. C., and Zhou, F. C. (1986a). Induced homotypic collateral sprouting of hippocampal serotonergic fibers. In: Gilad G. M., Gorio, A., and Kreutzberg, G. W. (eds), Processes of recovery from Neuronal Trauma Amsterdam: Elsevier, Exp. Brain Res. (Suppl 13 ), 129–141.

    Google Scholar 

  • Azmitia, E. C., and Zhou, F. C. (1986b). A specific serotonergic growth factor from 5,7-DHT lesioned hippocampus: in vitro evidence from dissociated cultures of raphe and locus ceruleus. Soc. Neurosci. Abst. 11: 1048.

    Google Scholar 

  • Azmitia, E. C., Buchan, A. M., and Williams, J. H. (1978). Structural and functional restoration by collateral sprouting of hippocampal 5-HT axons. Nature 274: 374–376.

    Article  Google Scholar 

  • Azmitia, E. C., Lama, P., Segal, M., Whitaker-Azmitia, P. M., Murphy, R. B., and Zhou, F. C. (1991). Effects of hippocampal supernatant extract on the development of serotonergic neurons in dissociated microcultures. Int. J. Develop. Neurosci. (In Press).

    Google Scholar 

  • Azmitia, E. C., Perlow, M. J., Brennan, M. J., and Lauder, J. M. (1981). Fetal raphe and hippocampal transplants into adult and aged C57BL/6N mice: A preliminary immunocytochemical study. Brain Res. Bull. 7: 703–710.

    Article  Google Scholar 

  • Barbin, G., Selak, I., Manthorpe, M., and Varon, S. (1984). Use of central neuronal cultures for detection of neuronotrophic agents. Neurosci. 12: 33–43.

    Article  Google Scholar 

  • Barde, Y.-A., Edgar, D., and Thoenen, H. (1980). Sensory neurons in culture: changing requirements for survival factors during embryonic development. Proc. Natl. Acad. Sci. USA 77: 1199–1203.

    Article  Google Scholar 

  • Barde, Y.-A., Edgar, D., and Thoenen, H. (1982). Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1: 549–553.

    Google Scholar 

  • Barde, Y.-A., Edgar, D., and Thoenen, H. (1983). New neurotrophic factors. Annu. Rev. Physiol. 45: 601–612.

    Article  Google Scholar 

  • Baumgarten, H. G., Jenner, S., and Klemin, H. P. (1981). Serotonin neurotoxins: Recent advances in the mode of administration and molecular mechanism of action. J. Physio. 77: 309–314.

    Google Scholar 

  • Bjorklund, A., and Gage, F. H. (1987). Grafts of fetal septal cholinergic neurons to the hippocampal formation in aged or Fimbria-Fornix-Lesioned rats. In: Azmitia, E. C., and Bjorklund, A. (eds), Cells and tissue transplantation into the adult brain. Annals of the New York Academy of Science. 495: 120–137.

    Google Scholar 

  • Bjorklund, A., and Stenevi, U. (1981). In vivo evidence for a hippocampal adrenergic neuronotrophic factor specifically released on septal deafferentation. Brain Res. 229: 403–428.

    Article  Google Scholar 

  • Bonyhady, R. E., Hendry, I. A., Hill, C. E., and McLennan, I. S. (1980). Characterization of a cardiac muscle factor required for the survival of cultured parasympathetic neurons. Neurosci. Lett. 18: 197–201.

    Article  Google Scholar 

  • Caday, C. G., Apostolides, P. J., Benowitz, L. I., Perrone-Bizzozero, N. I., and Finklestein, S. P. (1989). Partial purification and characterization of a neurite-promoting factor from the injured goldfish optic nerve. Molec. Brain Res. 5: 45–50.

    Article  Google Scholar 

  • Clewans, C., and Azmitia, E. C. (1984). Tryptophan hydroxylase in the hippocampus and midbrain following unilateral injection of 5,7-dihydroxytryptamine. Brain Res. 307: 125–133.

    Article  Google Scholar 

  • Cowan, W. M., Fawcett, J. W., Oleary, D. D. M., and Stanfield, B. B. (1984). Regressive events in neurogenesis. Science 225: 1258–1265.

    Article  Google Scholar 

  • Crutcher, K. A., and Collins, F. (1982). In vitro evidence for two distinct hippocampal growth factors: Basis of neuronal plasticity? Science 217: 67–68.

    Article  Google Scholar 

  • Crutcher, K. A., and Collins, F. (1986). Entorhinal lesions result in increased nerve growth factor-like growth-promoting activity in medium conditioned by hippocampal slices. Brain Res. 399: 383–389.

    Article  Google Scholar 

  • David, A. R., and Van Deusen, E. B. (1984). Recovery of enzyme markers for cholinergic terminals in septo-temporal regions of the hippocampus following selective fimbrial lesions in adult rat. Brain Res. 324: 119–128.

    Article  Google Scholar 

  • Ebendal, T. (1987). Comparative screening for ciliary neurotrophic activity in organs of the rat and chicken. J. Neurosci. Res. 17: 19–24.

    Article  Google Scholar 

  • Ebendal, T., Belew, M., Jacaboson, P.-O., and Porath, J. (1979). Neurite outgrowth elicited by embryonic chick heart: partial purification of the active factor. Neurosci. Lett. 14: 91–95.

    Article  Google Scholar 

  • Ebandal, T., Norrgren, G., and Hedlund, K.-O. (1983). Nerve growth-promoting activity in the chick embryo: quantitative aspects. Med. Biol. 61: 65–72.

    Google Scholar 

  • Edgar, D., Barde, T.-A., and Thoenen, H. (1981). Subpopulations of cultured chick sympathetic neurons differ in their requirements for survival factor. Nature, Lond. 289: 294–295.

    Article  Google Scholar 

  • Gage, F. H., Bjorklund, A., and Stenevi, U. (1983). Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholineergic and noradrenergic afferents. Brain Res. 268: 27–37.

    Article  Google Scholar 

  • Gage, F. H., Bjorklund, A., and Stenevi, U. (1984). Denervation releases a neuronal survival factor in adult rat hippocampus. Nature 308: 637–639.

    Article  Google Scholar 

  • Hadani, M., Harel, A., Solomon, A., Belkin, M., Lavie, V., and Schwartz, M. (1984). Substances originating from the optic nerve of neonatal rabbit induce regeneration-associated response in the injured optic nerve of adult rabbit. Proc. Natl. Acad. Sci. USA. 81: 7965–7969.

    Article  Google Scholar 

  • Hamburger, V. (1980). Trophic interactions in neurogenesis: a personal historical account. Ann. Rev. Neurosci. 3: 269–278.

    Article  Google Scholar 

  • Harper, G. P., and Thoenen, H. (1980). Nerve growth factor: Biological significance, measurement, and distribution. J. Neurochem. 34: 5–16.

    Article  Google Scholar 

  • Heacock, A. M., Schonfeld, A. R., and Katzman, R. (1986). Hippocampal neurotrophic factor: Characterization and response to denervation. Brain Res. 363: 299–306.

    Article  Google Scholar 

  • Hefti, F., Hartikka, J., and Knusel, B. (1989). Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases. Neurobiol. Aging. 10: 515–533.

    Article  Google Scholar 

  • Ignatius, M. J., Skene, J. H. P., Muller, H. W., and Shooter, E. M. (1987). Examination of a nerve injury-induced, 37 kDa protein: purification and characterization. Neurochem. Res. 12: 967–976.

    Article  Google Scholar 

  • Johnson, J. E., Barde, Y. A., Schwab, M., and Thoenen, H. (1986). Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. J. Neurosci. 6: 3031–3038.

    Google Scholar 

  • Kanakis, S. J., Hill, C. E., Hendry, I. A., and Watters, D. J. (1985). Sympathetic neuronal survival factors change after denervation. Developmental Brain Res. 20: 197–202.

    Article  Google Scholar 

  • Lauder, J. M., and Bloom, F. E. (1974). Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra. I. Cell Differentiation, J. Comp. Neurol. 155: 469–481.

    Article  Google Scholar 

  • Leibrock, J., Lottspeich, F., Hohn, A., Hofer, M., Hengerer, B., Masiakowski, P., Thoenen, H., and Barde, Y.-Al. (1989). Molecular cloning and expression of brain-derived neurotrophic factor. Naturé 341: 149–152.

    Article  Google Scholar 

  • Levi-Montalcini, R., and Angeletti, P. U. (1963). Essential role of the nerve growth factor in the survival and maintenance of dissociated sendory and sympathetic nerve cells in vitro. Dev. Biol. 7: 655–659.

    Google Scholar 

  • Longo, F. M., Manthrope, M., Skaper, S. D., Lundborg, G., and Varon, S. (1983). Neurotrophic activities in fluid accumulated in vivo within silicone nerve regeneration chambers. Brain Res. 261: 1099–1117.

    Article  Google Scholar 

  • Longo, F. M., Skaper, S. D., Manthorpe, M., Lundborg, G., and Varon, S. (1982). Further characterization of neuronotrophic factors accumulating in vivo within nerve stump-containing silicone chambers. Soc. Neurosci. Abst. 8: 861.

    Google Scholar 

  • Loesche, J., and Stewart, O. (1977). Behavioral correlents of denervation and reinnervation of the hippocampal formation of rat: Recovery of alternation performance following unilateral entorhinal cortex lesion. Brain Res. Bull. 2: 31–39.

    Article  Google Scholar 

  • Lund, R. D., and Lund, J. S. (1976). Plasticity in the developing visual system: the effects of retinal lesion made in young rats. J. Comp. Neurol. 169: 133–154.

    Article  Google Scholar 

  • Lundborg, G., Longo, F. M., and Varon, S. (1982). Nerve regeneration model and trophic factors in vivo. Brain Res. 232: 157–161.

    Article  Google Scholar 

  • Lynch, G., Gall, C., Rose, G., and Ctoman, C. W. (1976). Changes in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesion in the adult rat. Brain Res. 110: 57–61.

    Article  Google Scholar 

  • Manthrope, M., Nieto-Samoedro, M., Skaper, S. D., Lewis, E. R., Barbin, G., Longo, F. M., Cotman, C. W., and Varon, S. (1983). Neuronotrophic activity in brain wounds of the developing rat. Correlation with implant survival in the wound cavity. Brain Res. 267: 47–56.

    Article  Google Scholar 

  • Manthrope, M., Skaper, S. D., Adler, R., Landa, K. B., and Varon, S. (1980). Cholinergic neuronotrophic factors: IV Fractionation properties of an extract from selected chick embytonic eye tissue. J. Neurochem. 34: 69–75.

    Article  Google Scholar 

  • Manthrope, M., Skaper, S. D., Barbin, G., and Varon, S. (1982). Cholinergic neuronotrophic factors ( CNTFs ): VII Concurrent activities on certain nerve growth factor-responsive neurons. J. Neurochem. 38: 415–421.

    Article  Google Scholar 

  • Muller, H. W., Geibicke-Harter, P. J., Hangen, D. H., and Shooter, E. M. (1987). A specific 37,000-dalton protein that accumulates in regenerating but not in nonregenerating mammalian nerves. Science 228: 499–501.

    Article  Google Scholar 

  • Nakagawa, Y., and Ishihara, T. (1988). Enhancement of neurotrophic activity in cholinergic cells by hippocampal extract prepared from colchicine-lesioned rats. Brain Res. 439: 11–18.

    Article  Google Scholar 

  • Nakamura, Y., Mizuno, N., Konishi, A., and Sato, M. (1974). Synatpic reorganization of the red nucleus after chronic deafferentation from cerebellorubral fibers: an electron microscope study in the cat. Brain Res. 82: 298–301.

    Article  Google Scholar 

  • Needels, D. L., Nieto-Sampedro, M., and Cotman, C. W. (1987). Long-term support by injured brain extract of a subpopulation of ciliary ganglion neurons purified by differential adhesion. Neurochem. Res. 12: 901–907.

    Article  Google Scholar 

  • Nieto-Sampedro, M., Lewis, E. R., Cotman, C. W., Manthorpe, M., Skaper, S. D., Barbin, G., Longo, F. M., and Varon, S. (1982). Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion site. Science 217: 860–861.

    Article  Google Scholar 

  • Nieto-Sampedro, M., Manthorpe, M., Barbin, G., Varon, S., and Cotman, C. W. (1983). Injury-induced neuronotrophic activity in adult rat brain: Correlation with survival of delayed implants in the wound cavity. Neurosci. 3: 2219–2229.

    Google Scholar 

  • Nieto-Sampedro, M., Whittemore, Scott R., Needels, D. L., Larson, J., and Cotman, C. W. (1984). The survival of brain transplants is enhanced by extracts from injured brain. Proc. Natl. Acad. Sci. USA 81: 6250–6254.

    Article  Google Scholar 

  • Nishi, R., and Berg, D. K. (1977). Dissociated ciliary ganglion neurons in vitro: survival and synapse formation. Proc. Natl. Acad. Sci. U.S.A. 74: 5174–5175.

    Article  Google Scholar 

  • Nishi, R., and Berg, D. K. (1979). Survival and development of ciliary ganglion neurons grown alone in cell culture. Nature. 277: 232–234.

    Article  Google Scholar 

  • Nishi, R., and Berg, D. K. (1981). Two components from eye tissue that differentially stimulate the growth and development of ciliary ganglion neurons in cell culture. J. Neurosci. 1: 505–513.

    Google Scholar 

  • Scheff, S. W., and Cotman, C. W. (1977). Recovery of spontaneous alteration following lesion of entorhinal cortex in adult rats: Possible correlation to axon sprouting. Behay. Biol. 21: 286–293.

    Article  Google Scholar 

  • Schwartz, M., Belkin, M., Hard, A., Solomon, A., Valie, V., Hadani, M., Rachailovich, I., and Stein-Izsak, C. (1985). Regenerating fish optic nerves and a regeneration-like response in injured optic nerves of adult rabbits. Science 228: 600–603.

    Article  Google Scholar 

  • Skene, J. H. P., and Shooter, E. M. (1983). Denervated sheath cells secret a new protein after nerve injury. Proc. Natl. Acad. Sci. USA 80: 4169–4173.

    Article  Google Scholar 

  • Stenevi, U., Bjorkiund, A., and Moore, R. Y. (1972). Growth of intact central adrenergic axons in the denervated lateral geniculate body. Exp. Neurol. 35: 29–299.

    Article  Google Scholar 

  • Sternburger, L. A. (1979). Immunocytochemistry, 2nd edn., Wiley, New York, 104–169.

    Google Scholar 

  • Steward, O., and Loesche, J. (1977). Quantitative autoradiographic analysis of the time course of proliferation of contralateral entorhinal efferents in the dentate gyrus denervated by ipsilateral entorhinal lesions. Brain Res. 125: 11–21.

    Article  Google Scholar 

  • Steward, O., Cotman, C. W., and Lynch, G. A. (1976). A quantitative autoradiographic and electrophysiological study of the reinnervation of the dentate gyrus by contralateral entorhinal cortex following ipsilateral entorhinal lesions. Brain Res. 114: 181–200.

    Article  Google Scholar 

  • Thoenen, H., and Barde, Y.-A. (1980). Physiology of nerve growth factor. Physiol. Rev. 60: 1284–1335.

    Google Scholar 

  • Thoenen, H., and Edgar, D. (1985). Neurotrophic factors. Science 229: 238–242.

    Article  Google Scholar 

  • Turner, J. E., Barde, Y.-A., Schwab, M., and Thoenen, H. (1983). Extract from brain stimulates neurite outgrowth from fetal rat retinal explants. Dev Brain Res. 6: 77–84.

    Article  Google Scholar 

  • Watters, D., Belford, D., Hill, C., and Hendyr, I. (1989). Monoclonal antibody that inhibits biological activity of a mammalian cilaiary neurotrophic factor. J. Neurosci. Res. 22: 60–64.

    Article  Google Scholar 

  • Whittemore, S. R., Nieto-Sampedro, M., Needels, D. L., and Cotman, C. W. (1985). Neuronotrophic factors for mammalian brain neurons: Injury induction in neonatal, adult and aged rat brain. Develop. Brain Res. 20: 169–178.

    Article  Google Scholar 

  • Williams, L. R., Varon, S., Peterson, G. M., Wictorin, K., Fischer, W., Bjorklund, A., and Gage, F. H. (1986). Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transaction. Proc. Natl. Acad. Sci. USA 83: 9231–9235.

    Article  Google Scholar 

  • Zhou, F. C. (1988). Mechanical or chemical injury in the brain induces laminin production by astrocyte, Anat. Rec. 220: 108A.

    Google Scholar 

  • Zhou, F. C., Auerbach, S., and Azmitia, E. (1987a). Denervation of serotonergic fibers in the hippocampus induces a trophic factor which enhances the maturation of transplanted serotonergic neurons but not norepinephrinergic neurons. J. Neurosci. Res. 17: 235–246.

    Article  Google Scholar 

  • Zhou, F. C., Auerbach, S., Azmitia, E. C. (1987b). Injury of serotonergic fiber induces factor which promotes the maturation of serotonergic neurons but not norepinephrine neurons. In: Cell and Tissue transplantation into the Adult Brain. Azmitia, E. C., and Bjorklund, A. (eds), Ann. NY Acad. Sci. 495: 138–152.

    Google Scholar 

  • Zhou, F. C., Auerbch, S., Azmitia, E. C. (1988). Transplanted raphe and hippocampal fetal neurons do not displace the afferent inputs to the dorsal hippocampus from serotonergic neurons on the median raphe nucleus of the rat. Brain Res. 450: 51–59.

    Article  Google Scholar 

  • Zhou, F. C., and Azmitia, E. C. (1984). Induced homotypic collateral sprouting of serotonergic fibers in hippocampus. Brain Res. 308: 53–62.

    Article  Google Scholar 

  • Zhou, F. C., and Azmitia, E. C. (1985). The effect of adrenalectomy and corticosterone on homotypic collateral sprouting of serotonergic fibers in hippocampus. Neurosci. Lett. 54: 111–116.

    Article  Google Scholar 

  • Zhou, F. C., and Azmitia, E. C. (1986). Induced homotypic sprouting of serotonergic fibers in hippocampus: II, An immunocytochemical study. Brain Res. 373: 337–348.

    Article  Google Scholar 

  • Zhou, F. C., and Azmitia, E. C. (1990). Neurotrophic factor for serotonergic neurons prevent degeneration of grafted raphe neurons in the cerebellum. Brain Res. 507: 301–308.

    Article  Google Scholar 

  • Zhou, F. C., and Buchwald, N. (1989). Connectivities of the striatal grafts in adult rat brain: a rich afference and scant striato-nigral efference. Brain Res. 504: 15–30.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Indiana University, Indianapolis, IN, 46202, USA

    F. C. Zhou

  2. Department of Biology, New York University, NY, 10003, USA

    E. C. Azmitia

Authors
  1. F. C. Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. C. Azmitia
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Preclinical Research, Sandoz Pharma Ltd., P.O. Box 6, CH-4002, Basel, Switzerland

    John R. Fozard

  2. Institute of Pharmacology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands

    Pramod R. Saxena

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Zhou, F.C., Azmitia, E.C. (1991). A Neurotrophic Factor — SNTF — for Serotonergic Neurons. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7259-1_6

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7261-4

  • Online ISBN: 978-3-0348-7259-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation