Skip to main content
SpringerLink
Log in
Book cover

Neurotrophic Factors pp 1–31Cite as

Biological Roles of Neurotrophins

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 134))

Abstract

Neurotrophins are proteins that are structurally related and exert profound effects on cells of the nervous system. Four distinct neurotrophin genes have been identified in mice and in humans that encode for small dimeric, secretory proteins named nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5).

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

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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Airaksinen MS, Meyer M (1996) Most classes of dorsal root ganglion neurons are severely depleted but not absent in mice lacking neurotrophin-3. Neuroscience 73:907–911.

    PubMed  CAS  Google Scholar 

  • Airaksinen MS, Koltzenburg M, Lewin GR, Masu Y, Helbig C, Wolf E, Brem G, Toyka KV, Thoenen H, Meyer M (1996) Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation. Neuron 16:287–295.

    PubMed  CAS  Google Scholar 

  • Alcántara S, Frisén J, Del Río JA, Soriano E, Barbacid M, Silos-Santiago I (1997) TrkB signaling is required for postnatal survival of CNS neurons and protects hippocampal and motor neurons from axotomy-induced cell death. J Neurosci 17:3623–3633.

    PubMed  Google Scholar 

  • Allsopp TE, Wyatt S, Paterson HF, Davies AM (1993) The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 73:295–307.

    PubMed  CAS  Google Scholar 

  • Altar CA, Cai N, Bliven T, Juhasz M, Conner JM, Acheson AL, Lindsay RM, Wiegand SJ (1997) Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389:856–860.

    PubMed  CAS  Google Scholar 

  • Anton ES, Weskamp G, Reichardt LF, Matthew WD (1994) Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sei USA 91:2795–2799.

    CAS  Google Scholar 

  • Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA (1998) Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy(in press).

    Google Scholar 

  • Apfel SC, Wright DE, Wiideman AM, Dormia C, Snider WD, Kessler JA (1996) Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Mol Cell Neurosci 7:134–142.

    PubMed  CAS  Google Scholar 

  • Arenas E, Persson H (1994) Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature 367:368–371.

    PubMed  CAS  Google Scholar 

  • Barbacid M (1994) The trk family of neurotrophin receptors. J Neurobiol 25:1386–1403.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Barres BA, Raff MC, Gaese F, Bartke I, Dechant G, Barde YA (1994) A crucial role for neurotrophin-3 in oligodendrocyte development. Nature 367:371–375.

    PubMed  CAS  Google Scholar 

  • Bazan JF, Goodman CS (1997) Modular structure of the drosophila beat protein. Curr Biol 7:R338–339.

    PubMed  CAS  Google Scholar 

  • Berardi N, Cellerino A, Domenici L, Fagiolini M, Pizzorusso T, Cattaneo A, Maffei L (1994) Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system. Proc Natl Acad Sci USA 91:684–688.

    PubMed  CAS  Google Scholar 

  • Berkemeier LR, Winslow JW, Kaplan DR, Nikolics K, Goeddel DV, Rosenthal A (1991) Neurotrophin-5: A novel neurotrophic factor that activates trk and trkB. Neuron 7:857–866.

    PubMed  CAS  Google Scholar 

  • Berninger B, Garcia DE, Inagaki N, Hahnel C, Lindholm D (1993) BDNF and NT-3 induce intracellular Ca2+ elevation in hippocampal neurones. Neuroreport 4:1303–1306.

    PubMed  CAS  Google Scholar 

  • Bianchi LM, Conover JC, Fritzsch B, DeChiara T, Lindsay RM, Yancopoulos GD (1996) Degeneration of vestibular neurons in late embryogenesis of both heterozygous and homozygous BDNF null mutant mice. Development 122:1965–1973.

    PubMed  CAS  Google Scholar 

  • Birren SJ, Lo L, Anderson DJ (1993) Sympathetic neuroblasts undergo a developmental switch in trophic dependence. Development 119:597–610.

    PubMed  CAS  Google Scholar 

  • Blöchl A, Thoenen H (1995) Characterization of nerve growth factor (NGF) release from hippocampal neurons: Evidence for a constitutive and an unconventional sodium-dependent regulated pathway. Eur J Neurosci 7:1220–1228.

    PubMed  Google Scholar 

  • Blóchl A, Thoenen H (1996) Localization of cellular storage compartments and sites of constitutive and activity-dependent release of nerve growth factor (NGF) in primary cultures of hippocampal neurons. Mol Cell Neurosci 7:173–190.

    PubMed  Google Scholar 

  • Bovolenta P, Frade JM, Martí E, Rodríguez-Peña MA, Barde YA, Rodríguez-Tébar A (1996) Neurotrophin-3 antibodies disrupt the normal development of the chick retina. J Neurosci 16(14):4402–4410.

    PubMed  CAS  Google Scholar 

  • Bueker ED (1948) Implantation of tumors in the hind limb field of the embryonic chick and the developmental response of the lumbosacral nervous system. Anat Rec 102:369–390.

    PubMed  CAS  Google Scholar 

  • Cabelli RJ, Hohn A, Shatz CJ (1995) Inhibition of ocular dominance column formation by infusion of NT-4/5 or BDNF. Science 267:1662–1666.

    PubMed  CAS  Google Scholar 

  • Cabelli RJ, Shelton DL, Segal RA, Shatz CJ (1997) Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns. Neuron 19:63–76.

    PubMed  CAS  Google Scholar 

  • Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhäuser N, Böhm-Matthaei R, Baeuerle PA, Barde YA (1996) Selective activation of NF-kappaB by nerve growth factor through the neurotrophin receptor p75. Science 272:542–545.

    PubMed  CAS  Google Scholar 

  • Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 383:716–719.

    PubMed  CAS  Google Scholar 

  • Casanova J, Furriols M, McCormick A, Struhl G (1995) Similarities between trunk and spätzle, putative extracellular ligands specifying body pattern in Drosophila. Genes Dev 9:2539–2544.

    PubMed  CAS  Google Scholar 

  • Castrén E, Zafra F, Thoenen H, Lindholm D (1992) Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc Natl Acad Sci USA 89:9444–9448.

    PubMed  Google Scholar 

  • Causing CG, Gloster A, Aloyz R, Bamji SX, Chang E, Fawcett J, Kuchel G, Miller FD (1997) Synaptic innervation density is regulated by neuron-derived BDNF. Neuron 18:257–267.

    PubMed  CAS  Google Scholar 

  • Cellerino A, Maffei L (1996) The action of neurotrophins in the development of the visual system. Prog Neurobiol 49:53–71.

    PubMed  CAS  Google Scholar 

  • Cellerino A, Carroll P, Thoenen H, Barde YA (1997) Reduced size of retinal ganglion cell axons and hypomyelination in mice lacking brain-derived neurotrophic factor. Mol Cell Neurosci 9:397–408.

    PubMed  CAS  Google Scholar 

  • Chen KS, Nishimura MC, Armanini MP, Crowley C, Spencer SD, Phillips HS (1997) Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits. J Neurosci 17:7288–7296.

    PubMed  CAS  Google Scholar 

  • Cho HJ, Kim SY, Park MJ, Kim DS, Kim JK, Chu MY (1997) Expression of mRNA for brain-derived neurotrophic factor in the dorsal root ganglion following peripheral inflammation. Brain Res 749:358–362.

    PubMed  CAS  Google Scholar 

  • Cohen S (1960) Purification of a nerve-growth promoting protein from the mouse salivary gland and its neuro-cytotoxic antiserum. Proc Natl Acad Sci USA 46:302–311.

    PubMed  CAS  Google Scholar 

  • Cohen-Cory S, Fraser SE (1995) Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature 378:192–196.

    PubMed  CAS  Google Scholar 

  • Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P, Friedman B, Wiegand S, Vejsada R, Kato AC, DeChiara TM, Yancopoulos GD (1995) Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 375:235–238.

    PubMed  CAS  Google Scholar 

  • Croll SD, Wiegand SJ, Anderson KD, Lindsay RM, Nawa H (1994) Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF. Eur J Neurosci 6:1343–1353.

    PubMed  CAS  Google Scholar 

  • Crowley C, Spencer SD, Nishimura MC, Chen KS, Pitts-Meek S, Armanini MP, Ling LH, McMahon SB, Shelton DL, Levinson AD, Phillips HS (1994) Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 76:1001–1011.

    PubMed  CAS  Google Scholar 

  • Curtis R, Adryan KM, Stark JL, Park JS, Compton DL, Weskamp G, Huber LJ, Chao MV, Jaenisch R, Lee KF, Lindsay RM, Distefano PS (1995) Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins. Neuron 14:1201–1211.

    PubMed  CAS  Google Scholar 

  • Davies AM (1986) The survival and growth of embryonic proprioceptive neurons is promoted by a factor present in skeletal muscle. Dev Biol 115:55–67.

    Google Scholar 

  • Davies AM, Lindsay RM (1985) The cranial sensory ganglia in culture: differences in the response of placode-derived and neural crest-derived neurons to nerve growth factor. Dev Biol 111:62–72.

    CAS  Google Scholar 

  • Davies AM, Thoenen H, Barde YA (1986) Different factors from the central nervous system and periphery regulate the survival of sensory neurones. Nature 319:497–499.

    PubMed  CAS  Google Scholar 

  • Davies AM, Horton A, Burton LE, Schmelzer C, Vandlen R, Rosenthal A (1993a) Neurotrophin-4/5 is a mammalian-specific survival factor for distinct populations of sensory neurons. J Neurosci 13:4961–4967.

    PubMed  CAS  Google Scholar 

  • Davies AM, Lee KF, Jaenisch R (1993b) p75-deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins. Neuron 11:565–574.

    PubMed  CAS  Google Scholar 

  • Davies AM, Minichiello L, Klein R (1995) Developmental changes in NT3 signalling via TrkA and TrkB in embryonic neurons. EMBO J 14:4482–4489.

    PubMed  CAS  Google Scholar 

  • De Chaves EIP, Bussière M, Vance DE, Campenot RB, Vance JE (1997) Elevation of ceramide within distal neurites inhibits neurite growth in cultured rat sympathetic neurons. J Biol Chem 272:3028–3035.

    PubMed  Google Scholar 

  • Dechant G, Barde YA (1997) Signalling through the neurotrophin receptor p75NTR. Curr Opin Neurobiol 7:413–418.

    PubMed  CAS  Google Scholar 

  • Dechant G, Rodríguez-Tébar A, Kolbeck R, Barde YA (1993) Specific high-affinity receptors for neurotrophin-3 on sympathetic neurons. J Neurosci 13:2610–2616.

    PubMed  CAS  Google Scholar 

  • Dobrowsky RT, Werner MH, Castellino AM, Chao MV, Hannun YA (1994) Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. Science 265:1596–1599.

    PubMed  CAS  Google Scholar 

  • Dobrowsky RT, Jenkins GM, Hannun YA (1995) Neurotrophins induce sphingomyelin hydrolysis — Modulation by Co-expression of p75NTR with Trk receptors. J Biol Chem 270:22135–22142.

    PubMed  CAS  Google Scholar 

  • Domenici L, Cellerino A, Berardi N, Cattaneo A, Maffei L (1994) Antibodies to nerve growth factor (NGF) prolong the sensitive period for monocular deprivation in the rat. Neuroreport 5:2041–2044.

    PubMed  CAS  Google Scholar 

  • Driever W, Solnica-Krezel L, Schier AF, Neuhauss SCF, Malicki J, Stemple DL, Stainier DYR, Zwartkruis F, Abdelilah S, Rangini Z, Belak J, Boggs C (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123:37–46.

    PubMed  CAS  Google Scholar 

  • Dugich-Djordjevic MM, Tocco G, Lapchak PA, Pasinetti GM, Najm I, Baudry M, Hefti F (1992) Regionally specific and rapid increases in brain-derived neurotrophic factor messenger RNA in the adult rat brain following seizures induced by systemic administration of kainic acid. Neuroscience 47:303–315.

    PubMed  CAS  Google Scholar 

  • Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521.

    PubMed  CAS  Google Scholar 

  • ElShamy WM, Ernfors P (1996) A local action of neurotrophin-3 prevents the death of proliferating sensory neuron precursor cells. Neuron 16:963–972.

    PubMed  CAS  Google Scholar 

  • ElShamy WM, Linnarsson S, Lee KF, Jaenisch R, Ernfors P (1996) Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets. Development 122:491–500.

    PubMed  CAS  Google Scholar 

  • Erickson JT, Conover JC, Borday V, Champagnat J, Barbacid M, Yancopoulos G, Katz DM (1996) Mice lacking brain-derived neurotrophic factor exhibit visceral sensory neuron losses distinct from mice lacking NT4 and display a severe developmental deficit in control of breathing. J Neurosci 16:5361–5371.

    PubMed  CAS  Google Scholar 

  • Ernfors P, Persson H (1991) Developmentally regulated expression of HDNF/NT-3 mRNA in rat spinal cord motoneurons and expression of BDNF mRNA in embryonic dorsal root ganglion. Eur J Neurosci 3:953–961.

    PubMed  Google Scholar 

  • Ernfors P, Ibáñez CF, Ebendal T, Olson L, Persson H (1990a) Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: Developmental and topographical expression in the brain. Proc Natl Acad Sci USA 87:5454–5458.

    PubMed  CAS  Google Scholar 

  • Ernfors P, Wetmore C, Olson L, Persson H (1990b) Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron 5:511–526.

    PubMed  CAS  Google Scholar 

  • Ernfors P, Lee KF, Jaenisch R (1994a) Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature 368:147–150.

    PubMed  CAS  Google Scholar 

  • Ernfors P, Lee KF, Kucera J, Jaenisch R (1994b) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77:503–512.

    PubMed  CAS  Google Scholar 

  • Ernfors P, Van de Water T, Loring J, Jaenisch R (1995) Complementary roles of BDNF and NT-3 in vestibular and auditory development. Neuron 14:1153–1164.

    Google Scholar 

  • Fagan AM, Zhang H, Landis S, Smeyne RJ, Silos-Santiago I, Barbacid M (1996) TrkA, but not TrkC, receptors are essential for survival of sympathetic neurons in vivo. J Neurosci 16:6208–6218.

    PubMed  CAS  Google Scholar 

  • Falkenberg T, Mohammed AK, Henriksson B, Persson H, Winblad B, Lindefors N (1992) Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Neurosci Lett 138:153–156.

    PubMed  CAS  Google Scholar 

  • Fambrough D, Goodman CS (1996) The Drosophila beaten path gene encodes a novel secreted protein that regulates defasciculation at motor axon choice points. Cell 87:1049–1058.

    PubMed  CAS  Google Scholar 

  • Fariñas I, Jones KR, Backus C, Wang X-Y, Reichardt LF (1994) Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 369:658–661.

    PubMed  Google Scholar 

  • Fariñas I, Yoshida CK, Backus C, Reichardt LF (1996) Lack of neurotrophin-3 results in death of spinal sensory neurons and premature differentiation of their precursors. Neuron 17:1065–1078.

    PubMed  Google Scholar 

  • Fischer W, Wictorin K, Bjoerklund A, Williams LR, Varon S, Gage FH (1987) Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329:65–68.

    PubMed  CAS  Google Scholar 

  • Frade JM, Barde YA (1998) Microglia-derived nerve growth factor causes cell death in the developing retina. Neuron 20:35–41.

    PubMed  CAS  Google Scholar 

  • Frade JM, Rodríguez-Tébar A, Barde YA (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383:166–168.

    PubMed  CAS  Google Scholar 

  • Frade JM, Bovolenta P, Martínez-Morales JR, Arribas A, Barbas JA, Rodríguez-Tébar A (1997) Control of early cell death by BDNF in the chick retina. Development 124:3313–3320.

    PubMed  CAS  Google Scholar 

  • Friedel RH, Schnürch H, Stubbusch J, Barde YA (1997) Identification of genes differentially expressed by nerve growth factor- and neurotrophin-3-dependent sensory neurons. Proc Natl Acad Sei USA 94:12670–12675.

    CAS  Google Scholar 

  • Fritzsch B, Silos-Santiago I, Bianchi LM, Fariñas I (1997) The role of neurotrophic factors in regulating the development of inner ear innervation. TINS 20:159–164.

    PubMed  CAS  Google Scholar 

  • Funakoshi H, Belluardo N, Arenas E, Yamamoto Y, Casabona A, Persson H, Ibáñez CF (1995) Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Science 268:1495–1499.

    PubMed  CAS  Google Scholar 

  • Fundin BT, Silos-Santiago I, Ernfors P, Fagan AM, Aldskogius H, DeChiara TM, Phillips HS, Barbacid M, Yancopoulos GD, Rice FL (1997) Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and p75 LNGFR. Dev Biol 190:94–116.

    Google Scholar 

  • Gaese F, Kolbeck R, Barde YA (1994) Sensory ganglia require neurotrophin-3 early in development. Development 120:1613–1619.

    PubMed  CAS  Google Scholar 

  • Gagliardini V, Fernandez P-A, Lee RKK, Drexler HCA, Rotello RJ, Fishman MC, Yuan J (1994) Prevention of vertebrate neuronal death by the crmA gene. Science 263:826–828.

    PubMed  CAS  Google Scholar 

  • Gall CM, Isackson PJ (1989) Limbic seizures increase neuronal production of messenger RNA for nerve growth factor. Science 245:758–761.

    PubMed  CAS  Google Scholar 

  • Garcia I, Martinou I, Tsujimoto Y, Martinou J-C (1992) Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science 258:302–304.

    PubMed  CAS  Google Scholar 

  • Garofalo L, Ribeiro-da-Silva A, Cuello AC (1992) Nerve growth factor-induced synaptogenesis and hypertrophy of cortical cholinergic terminals. Proc Natl Acad Sei USA 89:2639–2643.

    CAS  Google Scholar 

  • Goodman LJ, Valverde J, Lim F, Geschwind MD, Federoff HJ, Geller AI, Hefti F (1996) Regulated release and polarized localization of brain-derived neurotrophic factor in hippocampal neurons. Mol Cell Neurosci 7:222–238.

    PubMed  CAS  Google Scholar 

  • Gorin PD, Johnson EM (1980) Effects of long-term nerve growth factor deprivation on the nervous system of the adult rat: an autoimmune approach. Brain Res 198:27–42.

    PubMed  CAS  Google Scholar 

  • Götz R, Raulf F, Schartl M (1992) Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution. J Neurochem 59:432–442.

    PubMed  Google Scholar 

  • Götz R, Köster R, Winkler C, Raulf F, Lottspeich F, Schartl M, Thoenen H (1994) Neurotrophin-6 is a new member of the nerve growth factor family. Nature 372:266–269.

    PubMed  Google Scholar 

  • Haffter P, Granato M, Brand M, Mullins MC, Hammerschmidt M, Kane DA, Odenthal J, Van Eeden FJM, Jiang YJ, Heisenberg CP, Kelsh RN, Furutani-Seiki M, Vogelsang E, Beuchle D, Schach U, Fabian C, Nüsslein-Volhard C (1996) The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123:1–36.

    PubMed  CAS  Google Scholar 

  • Hagg T, Manthorpe M, Vahlsing HL, Varon S (1988) Delayed treatment with nerve growth factor reverses the apparent loss of cholinergic neurons after acute brain damage. Exp Neurol 101:303–312.

    PubMed  CAS  Google Scholar 

  • Hallböök F, Ibáñez CF, Persson H (1991) Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6:1–20.

    Google Scholar 

  • Hefti F (1986) Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J Neurosci 6:2155–2162.

    PubMed  CAS  Google Scholar 

  • Herzog KH, Bailey K, Barde YA (1994) Expression of the BDNF gene in the developing visual system of the chick. Development 120:1643–1649.

    PubMed  CAS  Google Scholar 

  • Hofer MM, Barde YA (1988) Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature 331:261–262.

    PubMed  CAS  Google Scholar 

  • Hohn A, Leibrock J, Bailey K, Barde YA (1990) Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature 344:339–341.

    PubMed  CAS  Google Scholar 

  • Horvitz HR, Shaham S, Hengartner MO (1994) The genetics of programmed cell death in the nematode Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol 59:377–386.

    PubMed  CAS  Google Scholar 

  • Hory-Lee F, Russell M, Lindsay RM, Frank E (1993) Neurotrophin 3 supports the survival of developing muscle sensory neurons in culture. Proc Natl Acad Sci USA 90:2613–2617.

    PubMed  CAS  Google Scholar 

  • Huang B, Eberstadt M, Olejniczak ET, Meadows RP, Fesik SW (1996) NMR structure and mutagenesis of the FAS (APO-1/CD95) death domain. Nature 384:638–641.

    PubMed  CAS  Google Scholar 

  • Ibáñez CF, Ebendal T, Barbany G, Murray-Rust J, Blundell TL, Persson H (1992) Disruption of the low affinity receptor-binding site in NGF allows neuronal survival and differentiation by binding to trk gene product. Cell 69:329–341.

    PubMed  Google Scholar 

  • Ip NY, Ibáñez CF, Nye SH, McClain J, Jones PF, Gies DR, Belluscio L, Le Beau MM, Espinosa III R, Squinto SP, Persson H, Yancopoulos GD (1992) Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci USA 89:3060–3064.

    PubMed  CAS  Google Scholar 

  • Ip NY, Li Y, Yancopoulos GD, Lindsay RM (1993) Cultured hippocampal neurons show responses to BDNF, NT-3, and NT-4, but not NGF. J Neurosci 13:3394–3405.

    PubMed  CAS  Google Scholar 

  • Isackson PJ, Huntsman MM, Murray KD, Gall CM (1991) BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: Temporal patterns of induction distinct from NGF. Neuron 6:937–948.

    PubMed  CAS  Google Scholar 

  • Johnson EM, Gorin PD, Brandeis LD, Pearson J (1980) Dorsal root ganglion neurons are destroyed by exposure in utero to maternal antibodies to nerve growth factor. Science 210:916–918.

    PubMed  CAS  Google Scholar 

  • Jones KR, Reichardt LF (1990) Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Natl Acad Sci USA 87:8060–8064.

    PubMed  CAS  Google Scholar 

  • Jones KR, Fariñas I, Backus C, Reichardt LF (1994) Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 76:989–999.

    PubMed  CAS  Google Scholar 

  • Kaisho Y, Yoshimura K, Nakahama K (1990) Cloning and expression of a cDNA encoding a novel human neurotrophic factor. FEBS Lett 266:187–191.

    PubMed  CAS  Google Scholar 

  • Kalcheim C, Barde YA, Thoenen H, Le Douarin NM (1987) In vivo effect of brain- derived neurotrophic factor on the survival of developing dorsal root ganglion cells. EMBO J 6:2871–2873.

    PubMed  CAS  Google Scholar 

  • Kang H, Schuman EM (1995) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267:1658–1662.

    PubMed  CAS  Google Scholar 

  • Kang HJ, Schuman EM (1996) A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273:1402–1406.

    PubMed  CAS  Google Scholar 

  • Kim HG, Wang T, Olafsson P, Lu B (1994) Neurotrophin 3 potentiates neuronal activity and inhibits gamma-aminobutyratergic synaptic transmission in cortical neurons. Proc Natl Acad Sci USA 91:12341–12345.

    PubMed  CAS  Google Scholar 

  • Klein R, Parada LF, Coulier F, Barbacid M (1989) trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development. EMBO J 8:3701–3709.

    PubMed  CAS  Google Scholar 

  • Koliatsos VE, Clatterbuck RE, Winslow JW, Cayouette MH, Price DL (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10:359–367.

    PubMed  CAS  Google Scholar 

  • Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T. (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA 92:8856–8860.

    PubMed  CAS  Google Scholar 

  • Korte M, Griesbeck O, Gravel C, Carroll P, Staiger V, Thoenen H, Bonhoeffer T (1996) Virus-mediated gene transfer into hippocampal CA1 region restores long- term potentiation in brain-derived neurotrophic factor mutant mice. Proc Natl Acad Sci USA 93:12547–12552.

    PubMed  CAS  Google Scholar 

  • Kucera J, Ernfors P, Walro J, Jaenisch R (1995) Reduction in the number of spinal motor neurons in neurotrophin-3-deficient mice. Neuroscience 69:321–330.

    PubMed  CAS  Google Scholar 

  • Lauterborn J, Berschauer R, Gall C (1995) Cell-specific modulation of basal and seizure-induced neurotrophin expression by adrenalectomy. Neuroscience 68:363–378.

    PubMed  CAS  Google Scholar 

  • Le Douarin NM (1980) The ontogeny of the neural crest in chick embryo chimaeras. Nature 286:663–669.

    PubMed  Google Scholar 

  • Lee KF, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R (1992) Targeted mutation of the p75 low affinity NGF receptor gene leads to deficits in the peripheral sensory nervous system. Cell 69:737–749.

    PubMed  CAS  Google Scholar 

  • Lee KF, Davies AM, Jaenisch R (1994) p75-deficient embryonic dorsal root sensory and neonatal sympathetic neurons display a decreased sensitivity to NGF. Development 120:1027–1033.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lessmann V, Gottmann K, Heumann R (1994) BDNF and NT-4/5 enhance glutamatergic synaptic transmission in cultured hippocampal neurones. Neuroreport 6:21–25.

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini R (1980) Polydipsia after intracranial injections — a property of NGF or a contaminant? Nature 284:577.

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini R, Booker B (1960) Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve growth protein. Proc Natl Acad Sci USA 46:384–391.

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini R, Hamburger V (1953) A diffusible agent of mouse sarcoma producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo. J Exp Zool 123:233–278.

    Google Scholar 

  • Levi-Montalcini R, Meyer H, Hamburger V (1954) In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res 14:49–57.

    PubMed  CAS  Google Scholar 

  • Levine ES, Dreyfus CF, Black IB, Plummer MR (1995) Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Proc Natl Acad Sci USA 92:8074–8077.

    PubMed  CAS  Google Scholar 

  • Lewin GR, Koltzenburg M (1997) Rescue of cutaneous sensory neuron function in BDNF deficient mice by exogenous BDNF. Neuroscience Abstracts 667.12:1703.

    Google Scholar 

  • Lewin GR, Mendell LM (1993) Nerve growth factor and nociception. Trends Neurosci 16:353–359.

    PubMed  CAS  Google Scholar 

  • Lewin GR, Ritter AM, Mendell LM (1993) Nerve growth factor-induced hyperalgesia in the neonatal and adult rat. J Neurosci 13:2136–2148.

    PubMed  CAS  Google Scholar 

  • Liepinsh E, Hag LL, Otting G, Ibáñez CF (1997) NMR structure of the death domain of the p75 neurotrophin receptor. EMBO J 16:4999–5005.

    PubMed  CAS  Google Scholar 

  • Lindholm D, Hengerer B, Heumann R, Carroll P, Thoenen H (1990) Glucocorticoid hormones negatively regulate nerve growth factor expression in vivo and in cultured rat fibroblasts. Eur J Neurosci 2:795–801.

    PubMed  Google Scholar 

  • Lindholm D, Castrén E, Tsoulfas P, Kolbeck R, Da Penha Berzaghi M, Leingärtner A. Heisenberg CP, Tesarollo L, Parada LF, Thoenen H (1993) Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation. J Cell Biol 122:443–450.

    PubMed  CAS  Google Scholar 

  • Lindholm D, Castrén E, Berzaghi MP, Blöchl A, Thoenen H (1994) Activity-dependent and hormonal regulation of neurotrophin mRNA levels in the brain — implications for neuronal plasticity. J Neurobiol 25:1362–1372.

    PubMed  CAS  Google Scholar 

  • Lindsay RM (1988) Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons. J Neurosci 8:2394–2405.

    PubMed  CAS  Google Scholar 

  • Lindsay RM, Harmar AJ (1989) Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 337:362–364.

    PubMed  CAS  Google Scholar 

  • Liu X, Ernfors P, Wu H, Jaenisch R (1995) Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 375:238–241.

    PubMed  CAS  Google Scholar 

  • Lo DC, McAllister AK, Katz LC (1994) Neuronal transfection in brain slices using particle-mediated gene transfer. Neuron 13:1263–1268.

    PubMed  CAS  Google Scholar 

  • Lohof AM, Ip NY, Poo M (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363:350–353.

    PubMed  CAS  Google Scholar 

  • LoPresti P, Scott SA (1994) Target specificity and size of avian sensory neurons supported in vitro by nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3. J Neurobiol 25:1613–1624.

    PubMed  CAS  Google Scholar 

  • Lumsden AGS, Davies AM (1983) Earliest sensory nerve fibers are guided to peripheral targets by attractants other than nerve growth factor. Nature 306:786–788.

    PubMed  CAS  Google Scholar 

  • Mahadeo D, Kaplan L, Chao MV, Hempstead BL (1994) High affinity nerve growth factor binding displays a faster rate of association than pl40trk binding. Implications for multi-subunit polypeptide receptors. J Biol Chem 269:6884–6891.

    CAS  Google Scholar 

  • Majdan M, Lachance C, Gloster A, Aloyz R, Zeindler C, Bamji S, Bhakar A, Belliveau D, Fawcett J, Miller FD, Barker PA (1997) Transgenic mice expressing the intracellular domain of the p75 neurotrophin receptor undergo neuronal apoptosis. J Neurosci 17:6988–6998.

    PubMed  CAS  Google Scholar 

  • Mansour-Robaey S, Clarke DB, Wang Y-C, Bray GM, Aguayo AJ (1994) Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sei USA 91:1632–1636.

    CAS  Google Scholar 

  • Martin SC, Marazzi G, Sandell JH, Heinrich G (1995) Five Trk receptors in the zebrafish. Dev Biol 169:745–758.

    PubMed  CAS  Google Scholar 

  • Martinou JC, Dubois-Dauphin M, Staple JK, Rodriguez I, Frankowski H, Missotten M, Albertini P, Talabot D, Catsicas S, Pietra C, Huarte J (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13:1017–1030.

    PubMed  CAS  Google Scholar 

  • McAllister AK, Lo DC, Katz LC (1995) Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 15:791–803.

    PubMed  CAS  Google Scholar 

  • McAllister AK, Katz LC, Lo DC (1997) Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron 18:767–778.

    PubMed  CAS  Google Scholar 

  • McDonald NQ, Chao MV (1995) Structural determinants of neurotrophin action. J Biol Chem 270:19669–19672.

    PubMed  CAS  Google Scholar 

  • McDonald NQ, Hendrickson WA (1993) A structural superfamily of growth factorscontaining a cystine knot motif. Cell 73:421–424.

    PubMed  CAS  Google Scholar 

  • Meakin SO, Shooter EM (1992) The nerve growth factor family of receptors. TINS 15:323–331.

    PubMed  CAS  Google Scholar 

  • Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DLH, Yan Q, Priestley JV (1997) Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in tyrosine kinase A-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci 17:8476–8490.

    PubMed  CAS  Google Scholar 

  • Minichiello L, Klein R (1996) TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Genes Dev 10:2849–2858.

    PubMed  CAS  Google Scholar 

  • Morisato D, Anderson KV (1994) The Spätzle gene encodes a component of the extracellular signaling pathway establishing the dorso-ventral pattern of the Drosophila embryo. Cell:677–688.

    Google Scholar 

  • Nagata S (1997) Apoptosis by death factor. Cell 88:355–365.

    PubMed  CAS  Google Scholar 

  • Naumann T, Peterson GM, Frotscher M (1992) Fine structure of rat septohippocampal neurons:II. A time course analysis following axotomy. J Comp Neurol 325:219–242.

    CAS  Google Scholar 

  • Nawa H, Carnahan J, Gall C (1995) BDNF protein measured by a novel enzyme immunoassay in normal brain and after seizure: Partial disagreement with mRNA levels. Eur J Neurosci 7:1527–1535.

    PubMed  CAS  Google Scholar 

  • Neeper SA, Gómez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373:109 Neveu I, Arenas E (1996) Neurotrophins promote the survival and development of neurons in the cerebellum of hypothyroid rats in vivo. J Cell Biol 133:631–646.

    Google Scholar 

  • Oakley RA, Garner AS, Large TH, Frank E (1995) Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death. Development 121:1341–1350.

    PubMed  CAS  Google Scholar 

  • Ockel M, Lewin GR, Barde YA (1996) In vivo effects of neurotrophin-3 during sensory neurogenesis. Development 122:301–307.

    PubMed  CAS  Google Scholar 

  • Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14:453–501.

    PubMed  CAS  Google Scholar 

  • Otten U (1984) Nerve growth factor and the peptidergic sensory neurons. Trends Pharmacol Sei 5:307–310.

    CAS  Google Scholar 

  • Patterson SL, Grover LM, Schwartzkroin PA, Bothwell M (1992) Neurotrophin expression in rat hippocampal slices: A stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs. Neuron 9:1081–1088.

    PubMed  CAS  Google Scholar 

  • Patterson SL, Abel T, Deuel TAS, MArtin KC, Rose JC, Kandel ER (1996) Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 16:1137–1145.

    PubMed  CAS  Google Scholar 

  • Pearson J, Johnson EM, Brandeis L (1983) Effects of antibodies to nerve growth factor on intrauterine development of derivatives of cranial neural crest and placode in the guinea pig. Dev Biol 96:32–36.

    PubMed  CAS  Google Scholar 

  • Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M, Sinicropi D, Burton LE, Peroutka SJ (1994) The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 36:244–246.

    PubMed  CAS  Google Scholar 

  • Purves D (1988) Body and brain. A trophic theory of neural connections. Harvard University Press, Cambridge, Massachusetts.

    Google Scholar 

  • Purves D, Nja A (1976) Effect of nerve growth factor on synaptic depression after axotomy. Nature 260:535–536.

    PubMed  CAS  Google Scholar 

  • Rabizadeh S, Oh J, Zhong L, Yang J, Bitler CM, Butcher LL, Bredesen DE (1993) Induction of apoptosis by the low-affinity NGF receptor. Science 261:345–348.

    PubMed  CAS  Google Scholar 

  • Rice FL, Albers KM, Davis BM, Silos-Santiago I, Wilkinson GA, LeMaster AM, Ernfors P, Smeyne RJ, Aldskogius H, Phillips HS, Barbacid M, DeChiara TM, Yancopoulos GD, Fundin BT (1998). Differential dependency of unmyelinated and Aδ epidermal and upper dermal innervation on neurotrophins, trk receptors and p75LNGFR. Dev Biol (in press).

    Google Scholar 

  • Riddle DR, Lo DC, Katz LC (1995) NT-4-mediated rescue of lateral geniculate neurons from effects of monocular deprivation. Nature 378:189–191.

    PubMed  CAS  Google Scholar 

  • Rosenthal A, Goeddel DV, Nguyen T, Lewis M, Shih A, Laramee GR, Nikolics K, Winslow JW (1990) Primary structure and biological activity of a novel human neurotrophic factor. Neuron 4:767–773.

    PubMed  CAS  Google Scholar 

  • Ruit, KG, Osborne PA, Schmidt RE, Johnson EM Jr., Snider WD (1990) Nerve growth factor regulates sympathetic ganglion cell morphology and survival in the adult mouse. J Neurosci 10:2412–2419.

    PubMed  CAS  Google Scholar 

  • Rydén M, Murray-Rust J, Glass D, Ilag LL, Trupp M, Yancopoulos GD, McDonald NQ, Ibáñez CF (1995) Functional analysis of mutant neurotrophins deficient in low-affinity binding reveals a role for p75LNGFR in NT-4 signalling. EMBO J 14:1979–1990.

    PubMed  Google Scholar 

  • Rydén M, Hempstead B, Ibáñez CF (1997) Differential modulation of neuron survival during development by nerve growth factor binding to the p75 neurotrophin receptor. J Biol Chem 272:16322–16328.

    PubMed  Google Scholar 

  • Schäfer T, Schwab ME, Thoenen H (1983) Increased formation of preganglionic synapses and axons due to a retrograde trans-synaptic action of nerve growth factor in the rat sympathetic nervous system. J Neurosci 3:1501–1520.

    PubMed  Google Scholar 

  • Schimmang T, Minichiello L, Vazquez E, Jose IS, Giraldez F, Klein R, Represa J (1995) Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets. Development 121:3381–3391.

    PubMed  CAS  Google Scholar 

  • Schwartz PM, Borghesani PR, Levy RL, Pomeroy SL, Segal RA (1997) Abnormal cerebellar development and foliation in BDNF—/— mice reveals a role for neurotrophins in CNS patterning. Neuron 19:269–281.

    PubMed  CAS  Google Scholar 

  • Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde YA (1992) Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 360:757–759.

    PubMed  CAS  Google Scholar 

  • Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M (1994) The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 78:409–424.

    PubMed  CAS  Google Scholar 

  • Smeyne RJ, Klein R, Schnapp A, Long LK, Bryant S, Lewin A, Lira SA, Barbacid M (1994) Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 368:246–249.

    PubMed  CAS  Google Scholar 

  • Snider WD (1994) Functions of the neurotrophins during nervous system development: What the knockouts are teaching us. Cell 77:627–638.

    PubMed  Google Scholar 

  • Strohmaier C, Carter BD, Urfer R, Barde YA, Dechant G (1996) A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor. EMBO J 15:3332–3337.

    PubMed  CAS  Google Scholar 

  • Stucky CL, Koltzenburg M, Lindsay RM, Yancopoulos GD (1996) Neurotrophin-4 (NT-4) is required for the development of a subclass of cutaneous sensory neurons. Neuroscience Abstracts 396.5:992.

    Google Scholar 

  • Suen PC, Wu K, Levine ES, Mount HTJ, Xu JL, Lin SY, Black IB (1997) Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1. Proc Natl Acad Sei USA 94:8191–8195.

    CAS  Google Scholar 

  • Tessarollo L, Tsoulfas P, Martin-Zanca D, Gilbert DJ, Jenkins. NA, Copeland NG, Parada LF (1993) trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. Development 118:463–475.

    PubMed  CAS  Google Scholar 

  • Van der Zee CEEM, Ross GM, Riopelle RJ, Hagg T (1996) Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice. Science 274:1729–1732.

    PubMed  Google Scholar 

  • Verdi JM, Anderson DJ (1994) Neurotrophins regulate sequential changes in neurotrophin receptor expression by sympathetic neuroblasts. Neuron 13:1359–1372.

    PubMed  CAS  Google Scholar 

  • von Bartheld CS, Byers MR, Williams R, Bothwell M (1996). Anterograde transport of neurotrophins and axodendritic transfer in the developing visual system. Nature 379:830–833.

    Google Scholar 

  • Woolf CJ (1996) Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain. Philos Trans R Soc Lond B Biol Sei 351:441–448.

    CAS  Google Scholar 

  • Wyatt S, Piñón LGP, Ernfors P, Davies AM (1997) Sympathetic neuron survival and TrkA expression in NT3-deficient mouse embryos. EMBO J 16:3115–3123.

    PubMed  CAS  Google Scholar 

  • Yan Q, Elliott J, Snider WD (1992) Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360:753–755.

    PubMed  CAS  Google Scholar 

  • Yeo TT, Chua-Couzens J, Butcher LL, Bredesen DE, Cooper JD, Valletta JS, Mobley WC, Longo FM (1997) Absence of p75NTR causes increased basal forebrain cholinergic neuron size, choline acetyltransferase activity, and target innervation. J Neurosci 17:7594–7605.

    PubMed  CAS  Google Scholar 

  • Zafra F, Hengerer B, Leibrock J, Thoenen H, Lindholm D (1990) Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. EMBO J 9:3545–3550.

    PubMed  CAS  Google Scholar 

  • Zafra F, Castrén E, Thoenen H, Lindholm D (1991) Interplay between glutamate and gamma-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons. Proc Natl Acad Sci USA 88:10037–10041.

    PubMed  CAS  Google Scholar 

  • Zhou XF, Rush RA (1995) Sympathetic neurons in neonatal rats require endogenous neurotrophin-3 for survival. J Neurosci 15:6521–6530.

    PubMed  CAS  Google Scholar 

  • Zhou XF, Rush RA (1996) Endogenous brain-derived neurotrophic factor is antero- gradely transported in primary sensory neurons. Neurosci 74:945–953.

    CAS  Google Scholar 

Download references

Authors
  1. Y.-A. Barde
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Merck Sharp & Dohme, Neuroscience Research Centre, Terlings Park, CM20 2QR, Harlow, Essex, UK

    Franz Hefti Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Barde, YA. (1999). Biological Roles of Neurotrophins. In: Hefti, F. (eds) Neurotrophic Factors. Handbook of Experimental Pharmacology, vol 134. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59920-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59920-0_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64182-4

  • Online ISBN: 978-3-642-59920-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation