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Trophic Factors as Therapeutic Agents for Diseases Characterized by Neuronal Death

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Cell Death and Diseases of the Nervous System

Abstract

The unprecedented growth, over the last 20 yr, of information on the structure and function of the mammalian nervous system has generated high hopes for a more efficient management and treatment of nervous and mental disorders. A critical dimension of this development is the realization that the mature nervous system is much more capable of surviving and adapting to injury that once believed (1). Although there are multiple manifestations of the innate capability of the adult nervous system to adjust to injury (2), a remarkable indication of its regenerative potential is the presence, well within the adult life of mammalian species, of cells in the telencephalon that can differentiate into any type of neuron when given the proper instructive signals (3).

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References

  1. Ramon y Cajal S. Degeneration and Regeneration of the Nervous System. Oxford University Press, London, 1928.

    Google Scholar 

  2. Seil FJ. Neural Regeneration and Transplantation. Alan R. Liss, New York, 1988.

    Google Scholar 

  3. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992, 255: 1707–1710.

    Article  PubMed  CAS  Google Scholar 

  4. Loeb GE. Neural prosthetic interfaces with the nervous system. Trends Neurosci 1989, 12: 195–201.

    Article  PubMed  CAS  Google Scholar 

  5. Baldessarini RJ. Chemotherapy in Psychiatry. Principles and Practice. Harvard University Press, Cambridge, MA, 198

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Levi-Montalcini R, Hamburger V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 1951, 116: 321–361.

    Article  PubMed  CAS  Google Scholar 

  8. Gibbs CJ Jr, Gajdusek DC, Epstein LG, Asher DM, Goudsmit J. Animal models of human disease. Induction of persistent human T lymphotropic retrovirus infections in nonhuman primates and equines inoculated with tissues from AIDS patients or purified virus grown in vitro, in Animal Models of Retrovirus Infection and Their Relationship to AIDS (Salzman LA, ed.), Academic Press, Orlando, 1986, pp. 457–462.

    Google Scholar 

  9. Goedert M, Fine A, Dawbarn D, Wilcock GK, Chao MV. Nerve growth factor receptor mRNA distribution in human brain: normal levels in basal forebrain in Alzheimer’s disease. Mol Brain Res 1989, 5: 1–7.

    Article  PubMed  CAS  Google Scholar 

  10. Higgins GA, Mufson EJ. NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer’s disease. Exp Neurol 1989, 106: 222–236.

    Article  PubMed  CAS  Google Scholar 

  11. Ernfors P, Lindefors N, Chan-Palay V, Persson H. Cholinergic neurons of the nucleus basalis express elevated levels of nerve growth factor receptor mRNA in senile dementia of the Alzheimer type. Dementia 1990, 1: 138–145.

    Article  Google Scholar 

  12. Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 1991, 7: 695–702.

    Article  PubMed  CAS  Google Scholar 

  13. Koliatsos VE, Price DL, Clatterbuck RE, Markowska AL, Olton DS, Wilcox BJ. Neurotrophic strategies for treating Alzheimer’s disease: lessons from basic neurobiology and animal models. Ann NY Acad Sci 1993, 695: 292–299.

    Article  PubMed  CAS  Google Scholar 

  14. Faradji V, Sotelo J. Low serum levels of nerve growth factor in diabetic neuropathy. Acta Neurol Scand 1990, 81: 402–406.

    Article  PubMed  CAS  Google Scholar 

  15. Tooyama I, Kawamata Y, Walker D, Yamada T, Hanai K, Kimura H, Iwane M, Igarashi K, McGeer EG, McGeer PL. Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson’s disease. Neurology 1993, 43: 372–376.

    Article  PubMed  CAS  Google Scholar 

  16. Anand P, Terenghi G, Warner G, Kopelman P, Williams-Chestnut RE, Sinicropi DV. The role of endogenous nerve growth factor in human diabetic neuropathy. Nature Med 1996, 2: 703–707.

    Article  PubMed  CAS  Google Scholar 

  17. Higgins GA, Koh S, Chen KS, Gage FH. NGF induction of NGF receptor gene expression and cholinergic neuronal hypertrophy within the basal forebrain of the adult rat. Neuron 1989, 3: 247–256.

    Article  PubMed  CAS  Google Scholar 

  18. Holtzman DM, Li Y, Chen K, Gage FH, Epstein CJ, Mobley WC. Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age-related neurodegeneration. Neurology 1993, 43: 2668–2673.

    Article  PubMed  CAS  Google Scholar 

  19. Purves D. Body and Brain. Harvard University Press, Cambridge, 1988.

    Google Scholar 

  20. Lauder JM. Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Trends Neurosci 1993, 16: 233–240.

    Article  PubMed  CAS  Google Scholar 

  21. Ruegg MA, Tsim KWK, Horton SE. The agrin gene codes for a family of basal lamina proteins that differ in function and distribution. Neuron 1992, 8: 691–699.

    Article  PubMed  CAS  Google Scholar 

  22. Reist NE, Werle MJ, McMahan UJ. Agrin released by motor neurons induces the aggregation of acetylcholine receptors at neuromuscular junctions. Neuron 1992, 8: 865–868.

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  24. Ferguson IA, Schweitzer JB, Johnson EM Jr. Basic fibroblast growth factor: receptor-mediated internalization, metabolism, and anterograde axonal transport in retinal ganglion cells. J Neurosci 1990, 10: 2176–2189.

    PubMed  CAS  Google Scholar 

  25. Smith MA, Zhang L-X, Lyons WE, Mamounas LA. Anterograde transport of endogenous brain-derived neurotrophic factor in hippocampal mossy fibers. Neuroreport 1997, 8: 1829–1834.

    Article  PubMed  CAS  Google Scholar 

  26. Chan RS, Huey ED, Maecker HL, Cortopassi KM, Howard SA, Iyer AM, McIntosh LJ, Ajilore OA, Brooke SM, Sapolsky RM. Endocrine modulators of necrotic neuron death. Brain Pathol 1996, 6: 481–491.

    Article  PubMed  CAS  Google Scholar 

  27. Koliatsos VE. Biological therapies for Alzheimer’s disease: focus on trophic factors. Crit Rev Neurobiol 1996, 10: 205–238.

    Article  PubMed  CAS  Google Scholar 

  28. Growdon JH. Treatment of Alzheimer’s disease? N Engl J Med 1992, 18: 1306–1308.

    Article  Google Scholar 

  29. Growdon JH. Biological therapies for Alzheimer’s disease, in Dementia (Whitehouse PJ, ed.), F.A. Davis, Philadelphia, 1993, pp. 375–399.

    Google Scholar 

  30. Marin DB, Davis KL. Experimental Therapeutics, in Psychopharmacology: The Fourth Generation of Progress (Bloom FE, Kupfer DJ, eds.), Raven Press, Ltd. New York, 1995, pp. 1417–1426.

    Google Scholar 

  31. Atack JR. Cholinesterases in human degenerative diseases, in Cholinergic Basis for Alzheimer Therapy (Becker R, Giacobini E, eds.), Birkhäuser, Boston, 1991, pp. 31–37.

    Google Scholar 

  32. Giacobini E, Linville D, Messamore E, Ogane N. Toward a third generation of cholinesterase inhibitors, in Cholinergic Basis for Alzheimer Therapy (Becker R, Giacobini E, eds.), Birkhäuser, Boston, 1991, pp. 477–490.

    Google Scholar 

  33. Nordberg A, Lilja A, Lundqvist H, Hartvig P, Amberla K, Viitanen M, Warpman U, Johansson M, Hellström-Lindahl E, Bjurling P, Fasth K-J, Långström B, Winblad B. Tacrine restores cholinergic nicotinic receptors and glucose metabolism in Alzheimer patients as visualized by positron emission tomography. Neurobiol Aging 1992, 13: 747–758.

    Article  PubMed  CAS  Google Scholar 

  34. Davis KL, Thal LJ, Gamzu ER, Davis CS, Woolson RF, Gracon SI, Drachman DA, Schneider LS, Whitehouse PJ, Hoover TM, Morris JC, Kawas CH, Knopman DS, Earl NL, Kumar V, Doody RS, The Tacrine Collaborative Study Group. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease. N Engl J Med 1992, 327: 1253–

    Article  PubMed  CAS  Google Scholar 

  35. Knapp MJ, Pharma D, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. JAMA 1994, 271: 985–991.

    Article  PubMed  CAS  Google Scholar 

  36. Kang J, Lemaire H-G, Unterbeck A, Salbaum JM, Masters CL, Grzeschik K-H, Multhaup G, Beyreuther K, Müller-Hill B. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987, 325: 733–736.

    Article  PubMed  CAS  Google Scholar 

  37. Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuther K. Aggregation and secondary structure of synthetic amyloid A4 peptides of Alzheimer’s disease. J Mol Biol 1991, 218: 149–163.

    Article  PubMed  CAS  Google Scholar 

  38. Sisodia SS, Koo EH, Beyreuther K, Unterbeck A, Price DL. Evidence that β-amyloid protein in Alzheimer’s disease is not derived by normal processing. Science 1990, 248: 492–495.

    Article  PubMed  CAS  Google Scholar 

  39. Chartier-Harlin M-C, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J, Mullan M. Early-onset Alzheimer’s disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 1991, 353: 844–846.

    Article  PubMed  CAS  Google Scholar 

  40. Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J. Segregation of a mis-sense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991, 349: 704–706.

    Article  PubMed  CAS  Google Scholar 

  41. Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science 1991, 254: 97–99.

    Article  PubMed  CAS  Google Scholar 

  42. Karlinsky H, Vaula G, Haines JL, Ridgley J, Bergeron C, Mordila M, Tupler RG, Percy ME, Robitaille Y, Noldy NE, Yip TCK, Tanzi RE, Gusella JF, Becker R, Berg JM, Crapper McLachlan DR, St George-Hyslop PH. Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer’s disease and a mis-sense mutations in codon 717 of the β-amyloid precursor protein gene. Neurology 1992, 42: 1445–1453.

    Article  PubMed  CAS  Google Scholar 

  43. Whyte S, Beyreuther K, Masters CL. Rational therapeutic strategies for Alzheimer’s disease, in Neurodegenerative Diseases (Calne DB, ed.), W.B. Saunders, Philadelphia, 1994, pp. 647–664.

    Google Scholar 

  44. Haass C, Hung AY, Selkoe DJ. Processing of β-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. J Neurosci 1991, 11: 3783–3793.

    PubMed  CAS  Google Scholar 

  45. Cole GM, Huynh TV, Saitoh T. Evidence for lysosomal processing of amyloid β-protein precursor in cultured cells. Neurochem Res 1989, 14: 933–939.

    Article  PubMed  CAS  Google Scholar 

  46. McGeer PL, Akiyama H, Itagaki S, McGeer EG. Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci Lett 1989, 107: 341–346.

    Article  PubMed  CAS  Google Scholar 

  47. Troncoso JC, Sukhov RR, Kawas CH, Koliatsos VE. In situ labeling of dying cortical neurons in normal aging and in Alzheimer’s disease: correlations with senile plaques and disease progression. J Neuropathol Exp Neurol 1996, 55: 1134–1142.

    Article  PubMed  CAS  Google Scholar 

  48. Levi-Montalcini R, Hamburger V. A diffusible agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo. J ExpZool 1953, 123: 233–287.

    Google Scholar 

  49. Cohen S. Purification and metabolic effects of a nerve growth-promoting protein from snake venom. J Biol Chem 1959, 234: 1129–1137.

    PubMed  CAS  Google Scholar 

  50. Bocchini V, Angeletti PU. The nerve growth factor: purification as a 30,000-molecular-weight protein. Proc Natl Acad Sci USA 1969, 64: 787–794.

    Article  PubMed  CAS  Google Scholar 

  51. Angeletti RH, Bradshaw RA. Nerve growth factor from mouse submaxillary gland: amino acid sequence. Proc Natl Acad Sci USA 1971, 68: 2417–2420.

    Article  PubMed  CAS  Google Scholar 

  52. McDonald NQ, Lapatto R, Murray-Rust J, Gunning J, Wlodawer A, Blundell TL. New protein fold revealed by a 2,3-Å resolution crystal structure of nerve growth factor. Nature 1991, 354: 411–414.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  55. Ernfors P, Ibez CF, Ebendal T, Olson L, Persson H. 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 1990, 87: 5454–5458.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  58. Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 1990, 247: 1446–1451.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  61. Hallböök F, Ibáñez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 1991, 6: 845–858.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  63. Ibáñez CF. Neurotrophic factors: from structure-function studies to designing effective therapeutics. Trends BioTechnol 1995, 13: 217–227.

    Article  PubMed  Google Scholar 

  64. Hilton DJ. LIF: lots of interesting functions. Trends Biochem Sci 1992, 17: 72–76.

    Article  PubMed  CAS  Google Scholar 

  65. Lin L-FH, Mismer D, Lile JD, Armes LG, Butler ET III, Vannice JL, Collins F. Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). Science 1989, 246: 1023–1025.

    Article  PubMed  CAS  Google Scholar 

  66. Adler R, Landa KB, Manthorpe M, Varon S. Cholinergic neuronotrophic factors: intraocular distribution of trophic activity for ciliary neurons. Science 1979, 204: 1434–1436.

    Article  PubMed  CAS  Google Scholar 

  67. Stöckli KA, Lottspeich F, Sendtner M, Masiakowski P, Carroll P, Götz R, Lindholm D, Thoenen, H. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 1989, 342: 920–923.

    Article  PubMed  Google Scholar 

  68. Masu Y, Wolf E, Holtmann B, Sendtner M, Brem G, Thoenen H. Disruption of the CNTF gene results in motor neuron degeneration. Nature 1993, 365: 27–32.

    Article  PubMed  CAS  Google Scholar 

  69. Bazan JF. Neuropoietic cytokines in the hematopoietic fold. Neuron 1991, 7: 197–208.

    Article  PubMed  CAS  Google Scholar 

  70. Hall AK, Rao MS. Cytokines and neurokines: related ligands and related receptors. Trends Neurosci 1992, 15: 35–37.

    Article  PubMed  CAS  Google Scholar 

  71. Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren SJ, Yasukawa K, Kishimoto T, Anderson DJ, Stahl N, Yancopoulos GD. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp 130. Cell 1992, 69: 1121–1132.

    Article  PubMed  CAS  Google Scholar 

  72. Henderson JT, Seniuk NA, Richardson PM, Gauldie J, Roder JC. Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. J Clin Invest 1994, 93: 2632–2638.

    Article  PubMed  CAS  Google Scholar 

  73. Kessler JA, Ludlam WH, Freidin MM, Hall DH, Michaelson MD, Spray DC, Dougherty M, Batter DK. Cytokine-induced programmed death of cultured sympathetic neurons. Neuron 1993, 11: 1123–1132.

    Article  PubMed  CAS  Google Scholar 

  74. Pennica D, King KL, Shaw KJ, Luis E, Rullamas J, Luoh H-M, Darbonne WC, Knutzon DS, Yen R, Chien KR, Baker JB, Wood WI. Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci USA 1995, 92: 1142–1146.

    Article  PubMed  CAS  Google Scholar 

  75. Pennica D, Arce V, Swanson TA, Vejsada R, Pollock RA, Armanini M, Dudley K, Phillips HS, Rosenthal A, Kato AC, Henderson CE. Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term survival of spinal motoneurons. Neuron 1996, 17: 63–74.

    Article  PubMed  CAS  Google Scholar 

  76. Abraham JA, Whang JL, Tumolo A, Mergia A, Friedman J, Gospodarowicz D, Fiddes JC. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J 1986, 5: 2523–2528.

    PubMed  CAS  Google Scholar 

  77. Baird A, Böhlen P. Fibroblast growth factors, in Peptide Growth Factors and Their Receptors I (Sporn MB, Roberts AB, eds.), Springer-Verlag, New York, 1991.

    Google Scholar 

  78. Risau W. Developing brain produces an angiogenesis factor. Proc Natl Acad Sci USA 1986, 83: 3855–3859.

    Article  PubMed  CAS  Google Scholar 

  79. Rechler MM, Nissley SP. Insulin-like growth factors, in Peptide Growth Factors and Their Receptors I (Sporn MB, Roberts AB, eds.), Springer-Verlag, New York, 1991, pp. 263–367.

    Chapter  Google Scholar 

  80. Guler H-P, Zapf J, Froesch R. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med 1987, 317: 137–140.

    Article  PubMed  CAS  Google Scholar 

  81. Caroni P, Grandes P. Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors. J Cell Biol 1990, 110: 1307–1317.

    Article  PubMed  CAS  Google Scholar 

  82. Neff NT, Prevette D, Houenou LJ, Lewis ME, Glicksman MA, Yin QW, Oppenheim RW. Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival. J Neurobiol 1993, 24: 1578–1588.

    Article  PubMed  CAS  Google Scholar 

  83. Hughes RA, Sendtner M, Thoenen H. Members of several gene families influence survival of rat motoneurons in vitro and in vivo. J Neurosci Res 1993, 36: 663–671.

    Article  PubMed  CAS  Google Scholar 

  84. Schaar DG, Sieber B, A, Dreyfus CF, Black IB. Regional and cell-specific expression of GDNF in rat brain. Exp Neurol 1993, 124: 368–371.

    Article  PubMed  CAS  Google Scholar 

  85. Cameron VA, Nishimura E, Mathews LS, Lewis KA, Sawchenko PE, Vale WW. Hybridization histochemical localization of activin receptor subtyped in rat brain, pituitary, ovary, and testis. Endocrinology 1994, 134: 799–808.

    Article  PubMed  CAS  Google Scholar 

  86. Lin L-FH, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993, 260: 1130–1132.

    Article  PubMed  CAS  Google Scholar 

  87. Henderson CE, Phillips HS, Pollock RA, Davies AM, Lemeulle C, Armanini M, Simpson LC, Moffet B, Vandlen RA, Koliatsos VE, Rosenthal A. GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. Science 1994, 266: 1062—1064.

    Google Scholar 

  88. Oppenheim RW, Houenou LJ, Johnson JE, Lin L-FH, Li L, Lo AC, Newsome AL, Prevette DM, Wang S. Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature 1995, 373: 344–346.

    Article  PubMed  CAS  Google Scholar 

  89. Yan Q, Matheson C, Lopez OT. In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature 1995, 373: 341–344.

    Article  PubMed  CAS  Google Scholar 

  90. Beck KD, Valverde J, Alexi T, Poulsen K, Moffat B, Vandlen RA, Rosenthal A, Hefti F. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 1995, 373: 339–341.

    Article  PubMed  CAS  Google Scholar 

  91. Tomac A, Lindqvist E, Lin L-FH, Ögren SO, Young D, Hoffer BJ, Olson L. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 1995, 373: 335–339.

    Article  PubMed  CAS  Google Scholar 

  92. Krieglstein K, Suter-Crazzolara C, Fischer WH, Unsicker K. TGF-β superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity. EMBO J 1995, 14: 736–742.

    PubMed  CAS  Google Scholar 

  93. Kotzbauer PT, Lampe PA, Heuckeroth RO, Golden JP, Creedon DJ, Johnson EM Jr, Milbrandt J. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 1996, 384: 467–470.

    Article  PubMed  CAS  Google Scholar 

  94. Radeke MJ, Misko TP, Hsu C, Herzenberg LA, Shooter EM. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature 1987, 325: 593–597.

    Article  PubMed  CAS  Google Scholar 

  95. Rodriguez-Tébar A, Dechant G, Barde Y-A. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron 1990, 4: 487–492.

    Article  PubMed  Google Scholar 

  96. Meakin SO, Shooter EM. The nerve growth factor family of receptors. Trends Neurosci 1992, 15: 323–331.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  100. Frade JM, Rodriguez-Tébar A, Barde Y-A. Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 1996, 383: 166–168.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  103. Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M. Molecular and biochemical characterization of the human trk proto-oncogene. Mol Cell Biol 1989, 9: 24–33.

    PubMed  CAS  Google Scholar 

  104. Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF. The trk protooncogene product: a signal transducing receptor for nerve growth factor. Science 1991, 252: 554–558.

    Article  PubMed  CAS  Google Scholar 

  105. Chao MV. Neurotrophin receptors: a window into neuronal differentiation. Neuron 1992, 9: 583–593.

    Article  PubMed  CAS  Google Scholar 

  106. Davies AM, Lee K-F, Jaenisch R. p75-deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins. Neuron 1993, 11: 565–574.

    Article  PubMed  CAS  Google Scholar 

  107. Ehlers MD, Kaplan DR, Price DL, Koliatsos VE. NGF-stimulated retrograde transport of trkA in the mammalian nervous system. J Cell Biol 1995, 130: 149–156.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  110. Middlemas DS, Lindberg RA, Hunter T. trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors. Mol Cell Biol 1991, 11: 143—153.

    Google Scholar 

  111. Klein R, Smeyne RJ, Wurst W, Long LK, Auerbach BA, Joyner AL, Barbacid M. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell 1993, 75: 113–122.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  113. 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. Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 1995, 375: 235–238.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  115. Ernfors P, Lee K-F, Kucera J, Jaenisch. Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afférents. Cell 1994, 77: 503–512.

    Article  PubMed  CAS  Google Scholar 

  116. Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, Yancopoulos GD. LIFRβ and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 1993, 260: 1805–1808.

    Article  PubMed  CAS  Google Scholar 

  117. Davis S, Aldrich TH, Valenzuela DM, Wong V, Furth ME, Squinto SP, Yancopoulos GD. The receptor for ciliary neurotrophic factor. Science 1991, 253: 59–63.

    Article  PubMed  CAS  Google Scholar 

  118. Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, Ihle JN, Yancopoulos GD. Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 β receptor components. Science 1994, 263: 92–95.

    Article  PubMed  CAS  Google Scholar 

  119. DeChiara TM, Vejsada R, Poueymirou WT, Acheson A, Suri C, Conover JC, Friedman B, McClain J, Pan L, Stahl N, Ip NY, Kato A, Yancopoulos GD. Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuruon deficits at birth. Cell 1995, 83: 313–322.

    Article  PubMed  CAS  Google Scholar 

  120. Jing S, Wen D, Yu Y, Hoist PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis J-C, Hu S, Altrock BW, Fox GM. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-a, a novel receptor for GDNF. Cell 1996, 85: 1113–1124.

    Article  PubMed  CAS  Google Scholar 

  121. Treanor JJS, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A. Characterization of a multicomponent receptor for GDNF. Nature 1996, 382: 80–83.

    Article  PubMed  CAS  Google Scholar 

  122. Durbec P, Marcos-Gutierrez CV, Kilkenny C, Grigoriou M, Wartiowaara K, Suvanto P, Smith D, Ponder B, Costantini F, Saarma M, Sariola H, Pachnis V. GDNF signalling through the Ret receptor tyrosine kinase. Nature 1996, 381: 789–792.

    Article  PubMed  CAS  Google Scholar 

  123. Trupp M, Arenas E, Fainzilber M, Nilsson A, Sieber B, Grigoriou M, Kilkenny C, Salazar-Grueso E, Pachnis V, Arumäe U, Sariola H, Saarma M, Ibáñez CF. Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 1996, 381: 785–789.

    Article  PubMed  CAS  Google Scholar 

  124. Edery P, Lyonnet S, Mulligan LM, Pelet A, Dow E, Abel L, Holder S, Nihoul-Fékété, C, Ponder BAJ, Munnich A. Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994, 367: 378–380.

    Article  PubMed  CAS  Google Scholar 

  125. Romeo G, Ronchetto P, Luo Y, Barone V, Seri M, Ceccherini I, Pasini B, Bocciardi R, Lerone M, Kääriäinen H, Martucciello G. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994, 367: 377–378.

    Article  PubMed  CAS  Google Scholar 

  126. Hofstra RMW, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y, Pasini B, Höppener JWM, Ploos van Amstel HK, Romeo G, Lips CJM, Buys CHCM. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 1994, 367: 375–376.

    Article  PubMed  CAS  Google Scholar 

  127. Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 1994, 367: 380–383.

    Article  PubMed  CAS  Google Scholar 

  128. Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A. Renal and neuronal abnormalities in mice lacking GDNF. Nature 1996, 382: 76–79.

    Article  PubMed  CAS  Google Scholar 

  129. Popovic M, Jovanova-Nesic K, Popovic N, Bokonjic D, Dobric S, Rosic N, Rakic L. Behavioral and adaptive status in an experimental model of Alzheimer’s disease in rats. Int. J Neurosci 1996, 86: 281–299.

    Article  PubMed  CAS  Google Scholar 

  130. Sanchez M, Silos-Santiago I, Frisén J, He B, Lira SA, Barbacid M. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 1996, 382: 70–73.

    Article  PubMed  CAS  Google Scholar 

  131. Koliatsos VE, Price DL. Axotomy as an experimental model of neuronal injury and cell death. Brain Pathol 1996, 6: 447–465.

    Article  PubMed  CAS  Google Scholar 

  132. Lieberman AR. The axon reaction: a review of the principal features of perikaryal responses to axon injury, in International Review ofNeurobiology (Pfeiffer CC, Smythies JR, eds.), Academic Press, New York, 1971, pp. 49–124.

    Google Scholar 

  133. Snider WD, Elliott JL, Yan Q. Axotomy-induced neuronal death during development. J Neurobiol 1992, 23: 1231–1246.

    Article  PubMed  CAS  Google Scholar 

  134. Fritschy JM, Grzanna R. Restoration of ascending noradrenergic projections by residual locus coeruleus neurons: compensatory response to neurotoxic-induced cell death in the adult rat brain. J Comp Neurol 1992, 321: 421–441.

    Article  PubMed  CAS  Google Scholar 

  135. Coyle JT, Schwarcz R. Lesion of striatal neurones with kainic acid provides a model for Huntington’s chorea. Nature 1976, 263: 244–246.

    Article  PubMed  CAS  Google Scholar 

  136. Palmiter RD, Brinster RL. Germ-line transformation of mice. Annu Rev Genet 1986, 20: 465–499.

    Article  PubMed  CAS  Google Scholar 

  137. Capecchi MR. Altering the genome by homologous recombination. Science 1989, 244: 1288–1299.

    Article  PubMed  CAS  Google Scholar 

  138. Takahashi JS, Pinto LH, Hotz Vitaterna M. Forward and reverse genetic approaches to behavior in the mouse. Science 1994, 264: 1724–1733.

    Article  PubMed  CAS  Google Scholar 

  139. Scott MR, Köhler R, Foster D, Prusiner SB. Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci 1992, 1: 986–997.

    Article  PubMed  CAS  Google Scholar 

  140. Schedi A, Montoliu L, Kelsey G, Schütz G. A yeast artificial chromosome covering the tyrosinase gene confers copy number-dependent expression in transgenic mice. Nature 1993, 362: 258–261.

    Google Scholar 

  141. Price DL, Becher MW, Wong PC, Borchelt DR, Lee MK, Sisodia SS. Inherited neurode-generative diseases and transgenic models. Brain Pathol 1996, 6: 467–480.

    Article  PubMed  CAS  Google Scholar 

  142. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, Guido T, Hagopian S, Johnson-Wood K, Khan K, Lee M, Leibowitz P, Lieberburg I, Little S, Masliah E, McConlogue L, Montoya-Zavala M, Mucke L, Paganini L, Penniman E, Power M, Schenk D, Seubert P, Snyder B, Soriano F, Tan H, Vitale J, Wadsworth S, Wolozin B, Zhao J. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 1995, 373: 523–527.

    Article  PubMed  CAS  Google Scholar 

  143. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G. Correlative memory deficts, Aβ elevation and amyloid plaques in transgenic mice. Science 1996, 274: 99–102.

    Article  PubMed  CAS  Google Scholar 

  144. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng H-X, Chen W, Zhai P, Sufit RL, Siddique T. Motor neuron degeneration in mice that express a human Cu,Zn Superoxide dismutase mutation. Science 1994, 264: 1772–1775.

    Article  PubMed  CAS  Google Scholar 

  145. Burright EN, Clark HB, Servadio A, Matilla T, Feddersen RM, Yunis WS, Duvick LA, Zoghbi HY, Orr HT. SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell 1995, 82: 937–948.

    Article  PubMed  CAS  Google Scholar 

  146. Neurath MF, Pettersson S, Meyer zum Büschenfelde K-H, Straber W. Local administration of antisense phospohorothioate oligonuclotides to the p65 subunit of NF-kappaB abrogates established experimental colitis in mice. Nature Med 1996, 2: 998–1004.

    Article  PubMed  CAS  Google Scholar 

  147. Wilson MA, Tonegawa S. Synaptic plasticity, place cells and spatial memory: study with second generation knockouts. Trends Neurosci 1997, 20: 102–106.

    Article  PubMed  CAS  Google Scholar 

  148. Duchen LW, Strich SJ. An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant “wobbler.” J Neurol Neurosurg Psychiatry 1968, 31: 535–542.

    Article  PubMed  CAS  Google Scholar 

  149. Mitsumoto H, Bradley WG. Murine motor neuron disease (the wobbler mouse). Degeneration and regeneration of the lower motor neuron. Brain 1982, 105: 811–834.

    Article  PubMed  Google Scholar 

  150. Schmalbruch H, Jensen H-JS, Bjærg M, Kamieniecka Z, Kurland L. A new mouse mutant with progressive motor neuronopathy. J Neuropathol Exp Neurol 1991, 50: 192–204.

    Article  PubMed  CAS  Google Scholar 

  151. Price DL, Martin LJ, Sisodia SS, Walker LC, Voytko ML, Wagster MV, Cork LC, Koliatsos VE. The aged nonhuman primate. A model for the behavioral and brain abnormalities occurring in aged humans, in Alzheimer Disease (Terry RD, Katzman R, Bick KL, eds.), Raven Press, New York, 1994, pp. 231–245.

    Google Scholar 

  152. Koliatsos VE, Price DL. Retrograde axonal transport. Applications in trophic factor research, in Animal Models of Neurological Disorders (Boulton AA, Baker GB, Hefti F, eds.), Humana Press, Clifton, New Jersey, 1993, pp. 247–290.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  154. Walton M, Sirimanne E, Williams C, Gluckman P, Dragunow M. The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair. Mol Brain Res 1996, 43: 21–29.

    Article  PubMed  CAS  Google Scholar 

  155. Kromer LF. Nerve growth factor treatment after brain injury prevents neuronal death. Science 1987, 235: 214–216.

    Article  PubMed  CAS  Google Scholar 

  156. Koliatsos VE, Nauta HJW, Clatterbuck RE, Holtzman DM, Mobley WC, Price DL. Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey. J Neurosci 1990, 10: 3801–3813.

    PubMed  CAS  Google Scholar 

  157. Tuszynski MH, U, HS, Amarai DG, Gage FH. Nerve growth factor infusion in the primate brain reduces lesion-induced cholinergic neuronal degeneration. J Neurosci 1990, 10: 3604–3614.

    PubMed  CAS  Google Scholar 

  158. Wilcox BJ, Applegate MD, Portera-Cailliau C, Koliatsos VE. Nerve growth factor prevents apoptotic cell death in injured central cholinergic neurons. J Comp Neurol 1995, 359: 573–585.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  160. Markowska AL, Koliatsos VE, Breckler SJ, Price DL, Olton DS. Human nerve growth factor improves spatial memory in aged but not in young rats. J Neurosci 1994, 14: 4815–4824.

    PubMed  CAS  Google Scholar 

  161. Gage FH, Batchelor P, Chen KS, Chin D, Higgins GA, Koh S, Deputy S, Rosenberg MB, Fischer W, Bjorklund A. NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum. Neuron 1989, 2: 1177–1184.

    Article  PubMed  CAS  Google Scholar 

  162. Koliatsos VE, Applegate MD, Knüsel B, Junard EO, Burton LE, Mobley WC, Hefti FF, Price DL. Recombinant human nerve growth factor prevents retrograde degeneration of axotomized basal forebrain cholinergic neurons in the rat. Exp Neurol 1991, 112: 161–173.

    Article  PubMed  CAS  Google Scholar 

  163. Clatterbuck RE, Price DL, Koliatsos VE. Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system. Proc Natl Acad Sci USA 1993, 90: 2222–2226.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  165. Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ, Gerhardt GA. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996, 380: 252–255.

    Article  PubMed  CAS  Google Scholar 

  166. Choi-Lundberg DL, Lin Q, Chang Y-N, Chiang YL, Hay CM, Mohajeri H, Davidson BL, Bohn MC. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997, 275: 838–841.

    Article  PubMed  CAS  Google Scholar 

  167. Hagg T, Varon S. Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo. Proc Natl Acad Sci USA 1993, 90: 6315–6319.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  169. Koliatsos VE, Cayouette MH, Berkemeier LR, Clatterbuck RE, Price DL, Rosenthal A. Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons. Proc Natl Acad Sci USA 1994, 91: 3304–3308.

    Article  PubMed  CAS  Google Scholar 

  170. Yan Q, Matheson C, Lopez OT, Miller JA. The biological responses of axotomized adult motoneurons to brain-derived neurotrophic factor. J Neurosci 1994, 14: 5281–5291.

    PubMed  CAS  Google Scholar 

  171. Friedman B, Kleinfeld D, Ip NY, Verge VMK, Moulton R, Boland P, Zlotchenko E, Lindsay RM, Liu L. BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons. J Neurosci 1995, 15: 1044–1056.

    PubMed  CAS  Google Scholar 

  172. Mitsumoto H, Ikeda K, Holmlund T, Greene T, Cedarbaum JM, Wong V, Lindsay RM. The effects of ciliary neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann Neurol 1994, 36: 142–148.

    Article  PubMed  CAS  Google Scholar 

  173. Ikeda K, Wong V, Holmlund TH, Greene T, Cedarbaum JM, Lindsay RM, Mitsumoto H. Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron disease. Ann Neurol 1995, 37: 47–54.

    Article  PubMed  CAS  Google Scholar 

  174. Sagot Y, Tan SA, Hammang JP, Aebischer P, Kato AC. GDNF slows loss of motoneurons but not axonal degeneration or premature death of pmn/pmn mice. J Neurosci 1996, 16: 2335–2341.

    PubMed  CAS  Google Scholar 

  175. Wong J, Oblinger MM. NGF rescues substance P expression but not neurofilament or tubulin gene expression in axotomized sensory neurons. J Neurosci 1991, 11: 543–552.

    PubMed  CAS  Google Scholar 

  176. Yip HK, Johnson EM Jr. Developing dorsal root ganglion neurons require trophic support from their central processes: evidence for a role of retrogradely transported nerve growth factor from the central nervous system to the periphery. Proc Natl Acad Sci USA 1984, 81: 6245–6249.

    Article  PubMed  CAS  Google Scholar 

  177. Eriksson NP, Lindsay RM, Aldskogius H. BDNF and NT-3 rescue sensory but not motoneurones following axotomy in the neonate. Neuroreport 1994, 5: 1445–1448.

    PubMed  CAS  Google Scholar 

  178. Rich KM, Disch SP, Eichler ME. The influence of regeneration and nerve growth factor on the neuronal cell body reaction to injury. J Neurocytol 1989, 18: 569–576.

    Article  PubMed  CAS  Google Scholar 

  179. Hendry IA. The response of adrenergic neurones to axotomy and nerve growth factor. Brain Res 1975, 94: 87–97.

    Article  PubMed  CAS  Google Scholar 

  180. Manning PT, Russell JH, Simmons B, Johnson EM Jr. Protection from guanethidine-induced neuronal destruction by nerve growth factor: effect of NGF on immune function. Brain Res 1985, 340: 61–69.

    Article  PubMed  CAS  Google Scholar 

  181. Aloe L, Mugnaini E, Levi-Montalcini R. Light and electron microscopic studies on the excessive growth of sympathetic ganglia in rats injected daily from birth with 6-OHDA and NGF. Archives Italiennes De Biologie 113: 326–353.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  183. Diamond J, Holmes M, Coughlin M. Endogenous NGF and nerve impulses regulate the collateral sprouting of sensory axons in the skin of the adult rat. J Neurosci 1992, 12: 1454–1466.

    PubMed  CAS  Google Scholar 

  184. Penny GR, Afsharpour S, Kitai ST. The glutamate decarboxylase-, leucine enkephalin-, methionine enkephalin-and substance P-immunoreactive neurons in the neostriatum of the rat and cat: evidence for partial population overlap. Neuroscience 1986, 17: 1011–1045.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  186. Helgren ME, Cliffer KD, Torrente K, Cavnor C, Curtis R, DiStefano PS, Wiegand SJ, Lindsay RM. Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J Neurosci 1997, 17: 372–382.

    PubMed  CAS  Google Scholar 

  187. Mamounas LA, Blue ME, Siuciak JA, Altar CA. Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. J Neurosci 1995, 15: 7929–7939.

    PubMed  CAS  Google Scholar 

  188. Shigenaga MR, Park J-W, Cundy KC, Gimeno CJ, Ames BN. In vivo oxidative DNA damage: measurement of 8-hydroxy-2-deoxyguanosine in DNA and urine by high-performance liquid chormatography with electrochemical detection. Methods Enzymol 1990, 186: 521–530.

    Article  PubMed  CAS  Google Scholar 

  189. Apfel SC, Arezzo JC, Brownlee M, Federoff H, Kessler JA. Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res 1994, 634: 7–12.

    Article  PubMed  CAS  Google Scholar 

  190. Apfel SC, Lipton RB, Arezzo JC, Kessler JA. Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 1991, 29: 87–90.

    Article  PubMed  CAS  Google Scholar 

  191. Apfel SC, Arezzo JC, Lipson LA, Kessler JA. Nerve growth factor prevents experimental cisplatin neuropathy. Ann Neurol 1992, 31: 76–80.

    Article  PubMed  CAS  Google Scholar 

  192. Appel SH. A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. Ann Neurol 1981, 10: 499–505.

    Article  PubMed  CAS  Google Scholar 

  193. Hefti F, Weiner WJ. Nerve growth factor and Alzheimer’s disease. AnnNeurol 1986, 20: 275–281.

    CAS  Google Scholar 

  194. Sendtner M, Kreutzberg GW, Thoenen H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 1990, 345: 440–441.

    Article  PubMed  CAS  Google Scholar 

  195. Clatterbuck RE, Price DL, Koliatsos VE. Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons. J Comp Neurol 1994, 342: 45–56.

    Article  PubMed  CAS  Google Scholar 

  196. Shapiro L, Zhang X-X, Rupp RG, Wolff SM, Dinarello CA. Ciliary neurotrophic factor is an endogenous pyrogen. Proc Natl Acad Sci USA 1993, 90: 8614–8618.

    Article  PubMed  CAS  Google Scholar 

  197. Yuen EC, Mobley WC. Therapeutic potential of neurotrophic factors for neurological disorders. Ann Neurol 1996, 40: 346–354.

    Article  PubMed  CAS  Google Scholar 

  198. MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 1986, 321: 519–522.

    Article  PubMed  CAS  Google Scholar 

  199. Choi DW. Excitotoxic cell death. J Neurobiol 1992, 23: 1261–1276.

    Article  PubMed  CAS  Google Scholar 

  200. Frim DM, Uhler TA, Short MP, Ezzedine ZD, Klagsbrun M, Breakefield XO, Isacson O. Effects of biologically delivered NGF, BDNF and bFGF on striatal excitotoxic lesions. Neuroreport 1993, 4: 367–370.

    Article  PubMed  CAS  Google Scholar 

  201. Perez-Navarro E, Alberch J. Protective role of nerve growth factor against excitatory amino acid injury during neostriatal cholinergic neurons postnatal development. Exp Neurol 1995, 135: 146–152.

    Article  PubMed  CAS  Google Scholar 

  202. Liu Z, D’amore P, Mikati M, Gatt A, Holmes GL. Neuroprotective effect of chronic infusion of basic fibroblast growth factor on seizure-associated hippocampual damage. Brain Res 1993, 626: 335–338.

    Article  PubMed  CAS  Google Scholar 

  203. Lindholm D, Dechant G, Heisenberg CP, Thoenen H. Brain derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects against glutamate-induced neurotoxicity. Eur. J Neurosci 1993, 5: 1455–1464.

    Article  PubMed  CAS  Google Scholar 

  204. Albers GW, Goldberg MP, Choi DW. Af-methyl-D-aspartate antagonists: ready for clinical trial in brain ischemia? Ann Neurol 1989, 25: 398–403.

    Article  PubMed  CAS  Google Scholar 

  205. Diener PS, Bregman BS. Neurotrophic factors prevent the death of CNS neurons after spinal cord lesions in newborn rats. Neuroreport 1994, 5: 1913–1917.

    Article  PubMed  CAS  Google Scholar 

  206. Schnell L, Schneider R, Kolbeck R, Barde Y-A, Schwab ME. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 1994, 367: 170–173.

    Article  PubMed  CAS  Google Scholar 

  207. Cheng H, Cao Y, Olson L. Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science 1996, 273: 510–513.

    Article  PubMed  CAS  Google Scholar 

  208. Baffour R, Achanta K, Kaufman J, Berman J, Garb JL, Rhee S, Friedmann P. Synergistic effect of basic fibroblast growth factor and methylprednisolone on neurological function after experimental spinal cord injury. J Neurosurg 1995, 83: 105–110.

    Article  PubMed  CAS  Google Scholar 

  209. Faden AI. Experimental neurobiology of central nervous system trauma. Crit Rev Neurobiol 1993, 7: 175–186.

    PubMed  CAS  Google Scholar 

  210. Lyons WE, Fritschy JM, Grzanna R. The noradrenergic neurotoxin DSP-4 eliminates the coeruleospinal projection but spares projections of the A5 and A7 groups to the ventral horn of the rat spinal cord. J Neurosci 1989, 9: 1481–1489.

    PubMed  CAS  Google Scholar 

  211. Lyons MK, Anderson RE, Meyer FB. Basic fibroblast growth factor promotes in vivo cerebral angiogenesis in chronic forebrain ischemia. Brain Res 1991, 558: 315–320.

    Article  PubMed  CAS  Google Scholar 

  212. Blight AR. Remyelination, revascularization, and recovery of function in experimental spinal cord injury. Adv Neurol 1993, 59: 91–104.

    PubMed  CAS  Google Scholar 

  213. Levi-Montalcini R, Angeletti PU. Nerve growth factor. Physiol Rev 1968, 48: 534–569.

    PubMed  CAS  Google Scholar 

  214. Hollyday M, Hamburger V. Reduction of the naturally occurring motor neuron loss by enlargement of the periphery. J Comp Neurol 1976, 170: 311–320.

    Article  PubMed  CAS  Google Scholar 

  215. Davies AM, Bandtlow C, Heumann R, Korsching S, Rohrer H, Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature 1987, 326: 353–358.

    Article  PubMed  CAS  Google Scholar 

  216. Eide FF, Vining ER, Eide BL, Zang K, Wang X-Y, Reichardt LF. Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling. J Neurol Sci 1996, 16: 3123–3129.

    CAS  Google Scholar 

  217. Koliatsos VE, Price DL, Gouras GK, Cayouette MH, Burton LE, Winslow JW. Highly selective effects of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 on intact and injured basal forebrain magnocellular neurons. J Comp Neurol 1994, 343: 247–262.

    Article  PubMed  CAS  Google Scholar 

  218. Snider WD, Wright DE. Neurotrophins cause a new sensation. Neuron 1996, 16: 229–232.

    Article  PubMed  CAS  Google Scholar 

  219. Ruit KG, Elliott JL, Osborne PA, Yan Q, Snider WD. Selective dependence of mammalian dorsal root ganglion neurons on nerve growth factor during embryonic development. Neuron 1992, 8: 573–587.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  221. Prakash N, Cohen-Cory S, Frostig RD. Rapid and opposite effects of BDNF and NGF on the functional organization of the adult cortex in vivo. Nature 1996, 381: 702–706.

    Article  PubMed  CAS  Google Scholar 

  222. DiStefano PS, Friedman B, Radziejewski C, Alexander C, Boland P, Schick CM, Lindsay RM, Wiegand SJ. The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons. Neuron 1992, 8: 983–993.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  225. Conner JM, Lauterborn JC, Yan Q, Gall CM, Varon S. Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. J Neurosci 1997, 17: 2295–2313.

    PubMed  CAS  Google Scholar 

  226. Hamburger V, Brunso-Bechtold JK, Yip JW. Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor. J Neurosci 1981, 1: 60–71.

    PubMed  CAS  Google Scholar 

  227. Lumsden AGS, Davies AM. Earliest sensory nerve fibres are guided to peripheral targets ty attractants other than nerve growth factor. Nature 1983, 306: 786–788.

    Article  PubMed  CAS  Google Scholar 

  228. Oppenheim RW. The neurotrophic theory and naturally occurring motoneuron death. Trends Neurosci 1989, 12: 252–255.

    Article  PubMed  CAS  Google Scholar 

  229. Auburger G, Heumann R, Hellweg R, Korsching S, Thoenen H. Developmental changes of nerve growth factor and its mRNA in the rat hippocampus: comparison with choline acetyltransferase. Dev Biol 1987, 120: 322–328.

    Article  PubMed  CAS  Google Scholar 

  230. Hoyle GW, Mercer EH, Palmiter RD, Brinster RL. Expression of NGF in sympathetic neurons leads to excessive axon outgrowth from ganglia but decreased terminal innervation within tissues. Neuron 1993, 10: 1019–1034.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  232. Hofer MM, Barde Y-A. Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature 1988, 331: 261–262.

    Article  PubMed  CAS  Google Scholar 

  233. Sieber-Blum M. Role of the neurotrophic factors BDNF and NGF in the commitment of pluripotent neural crest cells. Neuron 1991, 6: 949–955.

    Article  PubMed  CAS  Google Scholar 

  234. Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, Lindsay RM, Yancopoulos GD. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 1990, 5: 501–509.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  236. Shelton DL, Sutherland J, Gripp J, Camerato T, Armanini MP, Phillips HS, Carroll K, Spencer SD, Levinson AD. Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins. J Neurosci 1995, 15: 477–491.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  238. Ernfors P, Bengzon J, Kokaia Z, Persson H, Lindvall O. Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. Neuron 1991, 7: 165–176.

    Article  PubMed  CAS  Google Scholar 

  239. Bengzon J, Kokaia Z, Ernfors P, Kokaia M, Leanza G, Nilsson OG, Persson H, Lindvall O. Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling. Neuroscience 1993, 53: 433–446.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  241. Takeda A, Onodera H, Sugimoto A, Kogure K, Obinata M, Shibahara S. Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia. Neuroscience 1993, 55: 23–31.

    Article  PubMed  CAS  Google Scholar 

  242. Riva M, Gale K, Mocchetti I. Basic fibroblast growth factor mRNA increases in specific brain regions following convulsive seizures. Mol Brain Res 1992, 15: 311–318.

    Article  PubMed  CAS  Google Scholar 

  243. Follesa P, Gale K, Mocchetti I. Regional and temporal pattern of expression of nerve growth factor and basic fibroblast growth factor mRNA in rat brain following electrocon-vulsive shock. Exp Neurol 1994, 127: 37–44.

    Article  PubMed  CAS  Google Scholar 

  244. Gall CM, Berschauer R, Isackson PJ. Seizures increase basic fibroblast growth factor mRNA in adult rat forebrain neurons and glia. Brain Res. Mol Brain Res 1994, 21: 190–205.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  246. Merlio J-P, Ernfors P, Kokaia Z, Middlemas DS, Bengzon J, Kokaia M, Smith M-L, Siejö, BK, Hunter T, Lindvall O, Persson H. Increased production of the TrkB protein tyrosine kinase receptor after brain insults. Neuron 1993, 10: 151–164.

    Article  PubMed  CAS  Google Scholar 

  247. Mudò, G, Persson H, Timmusk T, Funakoshi H, Bindoni M, Belluardo N. Increased expression of trkB and trkC messenger RNAs in the rat forebrain after focal mechanical injury. Neuroscience 1993, 57: 901–912.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  249. Ghosh A, Carnahan J, Greenberg ME. Requirement for BDNF in activity-dependent survival of cortical neurons. Science 1994, 263: 1618–1623.

    Article  PubMed  CAS  Google Scholar 

  250. Sarter M, Bruno JP. Trans-synaptic stimulation of cortical acetylcholine and enhancement of attentional functions: a rational approach for the development of cognition enhancers. Behav Brain Res 1997, 83: 7–14.

    Article  PubMed  CAS  Google Scholar 

  251. Yan Q, Matheson C, Sun J, Radeke MJ, Feinstein SC, Miller JA. Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression. Exp Neurol 1994, 127: 23–36.

    Article  PubMed  CAS  Google Scholar 

  252. Olsson Y. Vascular permeability in the peripheral nervous system, in Peripheral Neuropathy (Dyck PJ, Thomas PK, Lambert EH, Bunge R, eds.), W.B. Saunders, Philadelphia, 1984, pp. 579–597.

    Google Scholar 

  253. Fabrazzo M, Costa E, Mocchetti I. Stimulation of nerve growth factor biosynthesis in developing rat brain by reserpine: steroids as potential mediators. Mol Pharmacol 1991, 39: 144–149.

    PubMed  CAS  Google Scholar 

  254. Saporito MS, Brown ER, Hartpence KC, Wilcox HM, Robbins E, Vaught JL, Carswell S. Systemic dexamethasone administration increases septal Trk autopho-sphorylation in adult rats via an induction of nerve growth factor. Mol Pharmacol 1994, 45: 395–401.

    PubMed  CAS  Google Scholar 

  255. Barbany G, Persson H. Regulation of neurotrophin mRNA expression in the rat brain by glucocorticoids. Eur J Neurosci 1992, 4: 396–403.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  257. Mocchetti I, Spiga G, Hayes VY, Isackson PJ, Colangelo A. Glucocorticoids differentially increase nerve growth factor and basic fibroblast growth factor expression in the rat brain. J Neurosci 1996, 16: 2141–2148.

    PubMed  CAS  Google Scholar 

  258. Dugich-Djordjevic MM, Tocco G, Willoughby DA, Najm I, Pasinetti G, Thompson RF, Baudry M, Lapchak PA, Hefti F. BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity. Neuron 1992, 8: 1127–1138.

    Article  PubMed  CAS  Google Scholar 

  259. Chan KM, Lam DTN, Pong K, Widmer HR, Hefti F. Neurotrophin-4/5 treatment reduces infarct size in rats with middle cerebral artery occlusion. Neurochem Res 1996, 21: 763–767.

    Article  PubMed  CAS  Google Scholar 

  260. Schwartz JP, Costa E. Regulation of nerve growth factor content in C6 glioma cells by β-adrenergic receptor stimulation. Naunyn Schmiedebergs Arch Pharmacol 1977, 300: 123–129.

    Article  PubMed  CAS  Google Scholar 

  261. Follesa P, Mocchetti I. Regulation of basic fibroblast growth factor and nerve growth factor mRNA by β-adrenergic receptor activation and adrenal steroids in rat central nervous system. Mol Pharmacol 1993, 43: 132–138.

    PubMed  CAS  Google Scholar 

  262. Hayes VY, Isackson PJ, Fabrazzo M, Folleso P, Mocchetti I. Induction of nerve growth factor and basic fibroblast growth factor mRNA following clenbuterol: contrasting anatomical and cellular localization. Exp Neurol 1995, 132: 33–41.

    Article  PubMed  CAS  Google Scholar 

  263. Koizumi S, Contreras ML, Matsuda Y, Hama T, Lazarovici P, Guroff G. K-252a: a specific inhibitor of the action of nerve growth factor on PC12 cells. J Neurol Sci 1988, 8: 715–721.

    CAS  Google Scholar 

  264. Matsuda Y, Fukuda J. Inhibition by K-252a, a new inhibitor of protein kinase, of nerve growth factor-induced neurite outgrowth of chick embyro dorsal root ganglion cells. Neurosci Lett 1988, 87: 11–17.

    Article  PubMed  CAS  Google Scholar 

  265. Knüsel B, Hefti F. K-252 compounds: modulators of neurotrophin signal transduction. J Neurochem 1992, 59: 1987–1996.

    Article  PubMed  Google Scholar 

  266. Knüsel B, Rabin S, Widmer HR, Hefti F, Kaplan DR. Neurotrophin induced trk receptor phosphorylation and cholinergic neuron response in primary cultures of embryonic rat brain neurons. Neuroreport 1992, 3: 885–888.

    Article  PubMed  Google Scholar 

  267. Maroney AC, Sanders C, Neff NT, Dionne CA. K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR. J Neurochem 1997, 68: 88–94.

    Article  PubMed  CAS  Google Scholar 

  268. Suter U, Angst C, Tien C-L, Drinkwater CC, Lindsay RM, Shooter EM. NGF/BDNF chimeric proteins: analysis of neurotrophin specificity by homolog-scanning mutagenesis. J Neurosci 1992, 12: 306–318.

    PubMed  CAS  Google Scholar 

  269. Urfer R, Tsoulfas P, Soppet D, Escandon E, Parada LF, Presta LG. The binding epitopes of neurotrophin-3 to its receptors trkC and gp75 and the design of a multifunctional human neurotrophin. EMBO J 1994, 13: 5896–5909.

    PubMed  CAS  Google Scholar 

  270. Ilag LL, Curtis R, Glass D, Funakoshi H, Tobkes NJ, Ryan TE, Acheson A, Lindsay RM, Persson H, Yancopoulos GD, DiStefano PS, Ibáñez CF. Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo. Proc Natl Acad Sci USA 1995, 92: 607–611.

    Article  PubMed  CAS  Google Scholar 

  271. Deny DM, Wolfe LS. Gangliosides in isolated neurons and glial cells. Science 1967, 158: 1450–1452.

    Article  Google Scholar 

  272. Ferrari G, Batistatou A, Greene LA. Gangliosides rescue neuronal cells from death after trophic factor deprivation. J Neurosci 1993, 13: 1879–1887.

    PubMed  CAS  Google Scholar 

  273. Rabin SJ, Mocchetti I. GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 1995, 65: 347–354.

    Article  PubMed  CAS  Google Scholar 

  274. Cuello AC. Towards trophic factor pharmacology? Neurobiol Aging 1989, 10: 539–540.

    Article  PubMed  CAS  Google Scholar 

  275. Di Patre PL, Oh JD, Simmons JM, Butcher LL. Intrafimbrial colchicine produces transient impairment of radial-arm maze performance correlated with morphologic abnormalities of septohippocampal neurons expressing cholinergic markers and nerve growth factor receptor. Brain Res 1990, 523: 316–320.

    Article  PubMed  Google Scholar 

  276. Maysinger D, Filipovic-Greie J, Cuello CA. Effects of coencapsulated NGF and GM1 in rats with cortical lesions. J Neurochem 1993, 4: 971–974.

    CAS  Google Scholar 

  277. Silva RH, Felicio LF, Nasello AG, Vital MA, Frussa-Filho R. Effect of ganglioside (GM1) on memory in senescent rats. Neurobiol Aging 1996, 17: 583–586.

    Article  PubMed  CAS  Google Scholar 

  278. Hadjiconstantinou M, Weihmuller F, Neff NH. Treatment with GM1 ganglioside reverses dopamine D-2 receptor supersensitivity induced by the neurotoxin MPTP. Eur J Pharmacol 1989, 168: 261–264.

    Article  PubMed  CAS  Google Scholar 

  279. Schneider JS, Pope A, Simpson K, Taggart J, Smith MG, DiStefano L. Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment. Science 1992, 256: 843–846.

    Article  PubMed  CAS  Google Scholar 

  280. Favaron M, Manev H, Alho H, Bettolino M, Ferret B, Guidotti A, Costa E. Gangliosides prevent glutamate neurotoxicity in primary cultures of neonatal rat cerebellar and cortex. Proc Natl Acad Sci USA 1988, 85: 7351–7355.

    Article  PubMed  CAS  Google Scholar 

  281. Karpiac SE, Mahadick SP, Wakade CG. Ganglioside reduction of ischemic injury. CRC Crit Rev Clin Neurobiol 1990, 5: 221–237.

    Google Scholar 

  282. Seren MS, Rubini R, Lazzaro A, Zanoni R, Fiori MG, Leon A. Protective effects of a monosialoganglioside derivative following transitory forebrain ischemic in rats. Stroke 1990, 21: 1607–1612.

    Article  PubMed  CAS  Google Scholar 

  283. Lyons WE, George EB, Dawson TM, Steiner JP, Snyder SH. Immunosuppressan FK506 promotes neurite outgrowth in cultures of PC 12 cells and sensory ganglia. Proc Natl Acad Sci USA 1994, 91: 3191–3195.

    Article  PubMed  CAS  Google Scholar 

  284. Snyder SH, Sabatini DM. Immunophilins and the nervous system. Nature Med 1995, 1: 32–37.

    Article  PubMed  CAS  Google Scholar 

  285. Steiner JP, Hamilton GS, Ross DT, Valentine HL, Guo H, Connolly MA, Liang S, Ramsey C, Li JJ, Huang W, Howorth P, Soni R, Fuller M, Sauer H, Nowotnik AC, Suzdak PD. Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models. Proc Natl Acad Sci USA 1997, 94: 2019–2024.

    Article  PubMed  CAS  Google Scholar 

  286. Koliatsos VE, Price DL. Nonhuman primate models in trophic factor research, in Animal Models of Neurological Disorders (Boulton AA, Baker GB, Hefti F, eds.), Humana Press, Clifton, New Jersey, 1993, pp. 331–370.

    Google Scholar 

  287. Rosenberg MB, Friedmann T, Robertson RC, Tuszynski M, Wolff JA, Breakefield XO, Gage FH. Grafting genetically modified cells to the damaged brain: restorative effects of NGF expression. Science 1988, 242: 1575–1578.

    Article  PubMed  CAS  Google Scholar 

  288. Tseng JL, Baetge EE, Zurn AD, Aebischer P. GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine. J Neurosci 1997, 17: 325–333.

    PubMed  CAS  Google Scholar 

  289. Martinez-Serrano A, Fischer W, Bjorklund A. Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain. Neuron 1995, 15: 473–484.

    Article  PubMed  CAS  Google Scholar 

  290. Friden PM, Walus LR, Watson P, Doctrow SR, Kozarich JW, Bächman C, Bergman H, Hoffer B, Bloom F, Granholm A-C. Blood-brain barrier penetration and in vivo activity of an NGF conjugate. Science 1993, 259: 373–377.

    Article  PubMed  CAS  Google Scholar 

  291. Bäckman C, Rose GM, Hoffer BJ, Henry MA, Battus RT, Friden P, Granholm AC. Systemic administration of a nerve growth factor conjugate reverses age-related cognitive dysfunction and prevents cholinergic neuron atrophy. J Neurosci 1996, 16: 5437–5442.

    PubMed  Google Scholar 

  292. During MJ, Naegele JR, O’Malley KL, Geller AI. Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase. Science 1994, 266: 1399–1403.

    Article  PubMed  CAS  Google Scholar 

  293. Sukhov RR, Cayouette MH, Radeke MJ, Feinstein SC, Blumberg D, Rosenthal A, Price DL, Koliatsos VE. Evidence that perihypoglossal neurons involved in vestibular-auditory and gaze control functions respond to nerve growth factor. J Comp Neurol 1997, 383: 123–134.

    Article  PubMed  CAS  Google Scholar 

  294. Williams LR. Hypophagia is induced by intracerebroventricular administration of nerve growth factor. Exp Neurol 1991, 113: 31–37.

    Article  PubMed  CAS  Google Scholar 

  295. Glass DJ, Yancopoulos GD. The neurotrophins and their receptors. Trends Cell Biol 1993, 3: 262–268.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  297. Davis BM, Lewin GR, Mendell LM, Jones ME, Albers KM. Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli. Neuroscience 1993, 56: 789–792.

    Article  PubMed  CAS  Google Scholar 

  298. Della Seta D, de Acetis L, Aloe L, Alleva E. NGF effects on hot plate behaviors in mice. Pharmacol Biochem Behav 1994, 49: 701–705.

    Article  PubMed  CAS  Google Scholar 

  299. Andreev NY, Dimitrieva N, Koltzenburg M, McMahon SB. Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones. Pain 1995, 63: 109–115.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  301. Woolf CJ, Ma QP, Allchorne A, Poole S. Peripheral cell types contributing to the hyper-algesic action of nerve growth factor in inflammation. JNeurosci 1996, 16: 2716–2723.

    CAS  Google Scholar 

  302. Byers MR. Dynamic plasticity of dental sensory nerve structure and cytochemistry. Arch Oral Biol 1994, 39: 13–21.

    Article  Google Scholar 

  303. Woolf CJ, Safieh-Garabedian B, Ma QP, Crilly P, Winter J. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 1994, 62: 327–331.

    Article  PubMed  CAS  Google Scholar 

  304. Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ. Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. Br J Pharmacol 1995, 115: 1265–1275.

    Article  PubMed  CAS  Google Scholar 

  305. Harbaugh RE. Intracerebroventricularbethanechol chloride administration in Alzheimer’s disease. Ann NY Acad Sci 1988, 531: 174–179.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Vassilis E. Koliatsos
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  2. Italo Mocchetti
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Editors and Affiliations

  1. The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Vassilis E. Koliatsos MD

  2. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Rajiv R. Ratan MD, PhD

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Koliatsos, V.E., Mocchetti, I. (1999). Trophic Factors as Therapeutic Agents for Diseases Characterized by Neuronal Death. In: Koliatsos, V.E., Ratan, R.R. (eds) Cell Death and Diseases of the Nervous System. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1602-5_28

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  • DOI: https://doi.org/10.1007/978-1-4612-1602-5_28

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