Skip to main content
SpringerLink
Log in

Cell death in the nervous system

Lessons from insulin and insulin-like growth factors

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Programmed cell death is an essential process for proper neural development. Cell death, with its similar regulatory and executory mechanisms, also contributes to the origin or progression of many or even all neurodegenerative diseases. An understanding of the mechanisms that regulate cell death during neural development may provide new targets and tools to prevent neurodegeneration. Many studies that have focused mainly on insulin-like growth factor-I (IGF-I), have shown that insulin-related growth factors are widely expressed in the developing and adult nervous system, and positively modulate a number of processes during neural development, as well as in adult neuronal and glial physiology. These factors also show neuroprotective effects following neural damage. Although some specific actions have been demonstrated to be anti-apoptotic, we propose that a broad neuroprotective role is the foundation for many of the observed functions of the insulin-related growth factors, whose therapeutical potential for nervous system disorders may be greater than currently accepted.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kuan C.Y., Roth K.A., Flavell R.A., and Rakic P. (2000) Mechanisms of programmed cell death in the developing brain. Trends Neurosci. 23, 291–297.

    Article  PubMed  CAS  Google Scholar 

  2. Oppenheim R.W. (1991) Cell death during development of the nervous system. Annu. Rev. Neurosci. 14, 453–501.

    Article  PubMed  CAS  Google Scholar 

  3. Pettmann B. and Henderson C.E. (1998) Neuronal cell death. Neuron 20, 633–647.

    Article  PubMed  CAS  Google Scholar 

  4. Roth K.A. and D’Sa C. (2001) Apoptosis and brain development. Ment. Retard. Dev. Disabil. Res. Rev. 7, 261–266.

    Article  PubMed  CAS  Google Scholar 

  5. de la Rosa E.J. and de Pablo F. (2000) Cell death in early neural development: beyond the neurotrophic theory. Trends Neurosci. 23, 454–458.

    Article  PubMed  Google Scholar 

  6. Cameron H.A., Hazel T.G., and McKay R.D. (1998) Regulation of neurogenesis by growth factors and neurotransmitters. J. Neurobiol. 36, 287–306.

    Article  PubMed  CAS  Google Scholar 

  7. Raff M.C., Barres B.A., Burne J.F., Coles H.S., Ishizaki Y., and Jacobson M.D. (1993) Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262, 695–700.

    Article  PubMed  CAS  Google Scholar 

  8. Reichardt L.F. and Fariñas I. (1999), in Neurotrophins and the Neural Crest (Sieber-Blum M., ed.), (CRS Press, Boca Raton, FL), pp. 1–27.

    Google Scholar 

  9. Weiss E.R., Maness P., and Lauder J.M. (1998) Why do neurotransmitters act like growth factors? Perspect. Dev. Neurobiol. 5, 323–335.

    PubMed  CAS  Google Scholar 

  10. Dunker N., Schuster N., and Krieglstein K. (2001) TGF-beta modulates programmed cell death in the retina of the developing chick embryo. Development 128, 1933–1942.

    PubMed  CAS  Google Scholar 

  11. Frade J.M., Rodriguez-Tebar A., and Barde Y.A. (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383, 166–168.

    Article  PubMed  CAS  Google Scholar 

  12. Frago L.M., Leon Y., de la Rosa E.J., Gomez-Munoz A., and Varela-Nieto I. (1998) Nerve growth factor and ceramides modulate cell death in the early developing inner ear. J. Cell Sci. 111, 549–556.

    PubMed  CAS  Google Scholar 

  13. Frago L.M., Cañon S., de la Rosa E.J., Leon Y., and Varela-Nieto I. (2003) Programmed cell death in the developing inner ear is balanced by nerve growth factor and insulin-like growth factor I. J. Cell Sci. 116, 475–486.

    Article  PubMed  CAS  Google Scholar 

  14. Furuta Y., Piston D.W., and Hogan B.L. (1997) Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124, 2203–2212.

    PubMed  CAS  Google Scholar 

  15. D’Mello S.R. (1998) Molecular regulation of neuronal apoptosis. Curr. Top. Dev. Biol. 39, 187–213.

    Article  PubMed  CAS  Google Scholar 

  16. Joza N., Kroemer G., and Penninger J.M. (2002) Genetic analysis of the mammalian cell death machinery. Trends Genet. 18, 142–149.

    Article  PubMed  CAS  Google Scholar 

  17. Strasser A., O’Connor L., and Dixit V.M. (2000) Apoptosis signaling. Annu. Rev. Biochem. 69, 217–245.

    Article  PubMed  CAS  Google Scholar 

  18. Burek M.J. and Oppenheim R.W. (1996) Programmed cell death in the developing nervous system. Brain Pathol. 6, 427–446.

    PubMed  CAS  Google Scholar 

  19. Martin L.J. (2001) Neuronal cell death in nervous system development, disease, and injury. Int. J. Mol. Med. 7, 455–478.

    PubMed  CAS  Google Scholar 

  20. Mattson M.P. (2000) Apoptosis in neurodegenerative disorders. Nat. Rev. Mol. Cell Biol. 1, 120–129.

    Article  PubMed  CAS  Google Scholar 

  21. Nicholson D.W. (2000) From bench to clinic with apoptosis-based therapeutic agents. Nature 407, 810–816.

    Article  PubMed  CAS  Google Scholar 

  22. Nijhawan D., Honarpour N., and Wang X. (2000) Apoptosis in neural development and disease. Annu. Rev. Neurosci. 23, 73–87.

    Article  PubMed  CAS  Google Scholar 

  23. Yuan J. and Yankner B.A. (2000) Apoptosis in the nervous system. Nature 407, 802–809.

    Article  PubMed  CAS  Google Scholar 

  24. Bottenstein J.E. and Sato G.H. (1979) Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc. Natl. Acad. Sci. USA 76, 514–517.

    Article  PubMed  CAS  Google Scholar 

  25. Bottenstein J.E., Skaper S.D., Varon S.S., and Sato G.H. (1980) Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. Exp. Cell Res. 125, 183–190.

    Article  PubMed  CAS  Google Scholar 

  26. Vicario-Abejon C., Johe K.K., Hazel T.G., Collazo D., and McKay R.D. (1995) Functions of basic fibroblast growth factor and neurotrophins in the differentiation of hippocampal neurons. Neuron 15, 105–114.

    Article  PubMed  CAS  Google Scholar 

  27. D’Ercole A.J., Ye P., Calikoglu A.S., and Gutierrez-Ospina G. (1996) The role of the insulin-like growth factors in the central nervous system. Mol. Neurobiol. 13, 227–255.

    PubMed  CAS  Google Scholar 

  28. Anlar B., Sullivan K.A., and Feldman E.L. (1999) Insulin-like growth factor-I and central nervous system development. Horm. Metab Res. 31, 120–125.

    PubMed  CAS  Google Scholar 

  29. de Pablo F. and de la Rosa E.J. (1995) The developing CNS: a scenario for the action of proinsulin, insulin and insulin-like growth factors. Trends Neurosci. 18, 143–150.

    Article  PubMed  Google Scholar 

  30. Allan G.J., Flint D.J., and Patel K. (2001) Insulin-like growth factor axis during embryonic development. Reproduction 122, 31–39.

    Article  PubMed  CAS  Google Scholar 

  31. Bevan P. (2001) Insulin signalling. J. Cell Sci. 114, 1429–1430.

    PubMed  CAS  Google Scholar 

  32. LeRoith D., Werner H., Beitner-Johnson D., and Roberts C.T., Jr. (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr. Rev. 16, 143–163.

    Article  PubMed  CAS  Google Scholar 

  33. Vincent A. and Feldman E. (2002) Control of cell survival by IGF signaling pathways. Growth Horm. IGF Res. 12, 193.

    Article  PubMed  CAS  Google Scholar 

  34. Braeckman B.P., Houthoofd K., and Vanfleteren J.R. (2001) Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis elegans. Mech. Ageing Dev. 122, 673–693.

    Article  PubMed  CAS  Google Scholar 

  35. Brogiolo W., Stocker H., Ikeya T., Rintelen F., Fernandez R., and Hafen E. (2001) An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 20, 213–221.

    Article  Google Scholar 

  36. Cao C. and Brown M.R. (2001) Localization of an insulin-like peptide in brains of two flies. Cell Tissue Res. 304, 317–321.

    Article  PubMed  CAS  Google Scholar 

  37. Claeys I., Simonet G., Poels J., Van Loy T., Vercammen L., De Loof A., et al. (2002) Insulin-related peptides and their conserved signal transduction pathway. Peptides 23, 807–816.

    Article  PubMed  CAS  Google Scholar 

  38. Garofalo R.S. (2002) Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol. Metab. 13, 156–162.

    Article  PubMed  CAS  Google Scholar 

  39. Ikeya T., Galic M., Belawat P., Nairz K., and Hafen E. (2002) Nutrient-dependent expression of insulin-like peptides from neuroen-docrine cells in the CNS contributes to growth regulation in Drosophila. Curr. Biol. 12, 1293.

    Article  PubMed  CAS  Google Scholar 

  40. Leevers S.J. (2001) Growth control: invertebrate insulin surprises! Curr. Biol. 20, R209-R212.

    Article  Google Scholar 

  41. Oldham S., Stocker H., Laffargue M., Wittwer F., Wymann M., and Hafen E. (2002) The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development 129, 4103–4109.

    PubMed  CAS  Google Scholar 

  42. Pierce S.B., Costa M., Wisotzkey R., Devadhar S., Homburger S.A., Buchman A.R., et al. (2001) Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev. 15, 672–686.

    Article  PubMed  CAS  Google Scholar 

  43. Wolkow C.A., Kimura K.D., Lee M.S., and Ruvkun G. (2000) Regulation of C. elegans life-span by insulin-like signaling in the nervous system. Science 290, 147–150.

    Article  PubMed  CAS  Google Scholar 

  44. Hernandez-Sanchez C., Rubio E., Serna J., de la Rosa E.J., and de Pablo F. (2002) Unprocessed proinsulin promotes cell survival during neurulation in the chick embryo. Diabetes 51, 770–777.

    Article  PubMed  CAS  Google Scholar 

  45. Jones J.I. and Clemmons D.R. (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. 16, 3–34.

    Article  PubMed  CAS  Google Scholar 

  46. LeRoith D. and Bondy C. (1996), in Growth Factors and Cytokines in Health and Disease (LeRoith D. and Bondy C., eds.), (JAI Press, Greenwich, CT), pp. 1–26.

    Google Scholar 

  47. Serna J., Gonzalez-Guerrero P.R., Scanes C.G., Prati M., Morreale G., and de Pablo F. (1996) Differential and tissue-specific regulation of (pro)insulin and insulin-like growth factor-I mRNAs and levels of thyroid hormones in growth-retarded embryos. Growth Regul. 6, 73–82.

    PubMed  CAS  Google Scholar 

  48. Federici M., Porzio O., Zucaro L., Fusco A., Borboni P., Lauro D., et al. (1997) Distribution of insulin/insulin-like growth factor-I hybrid receptors in human tissues. Mol. Cell. Endocrinol. 129, 121–126.

    Article  PubMed  CAS  Google Scholar 

  49. Garcia-de Lacoba M., Alarcon C., de la Rosa E.J., and de Pablo F. (1999) Insulin/insulin-like growth factor-I hybrid receptors with high affinity for insulin are developmentally regulated during neurogenesis. Endocrinology 140, 233–243.

    Article  PubMed  CAS  Google Scholar 

  50. Hitchcock P.F., Otteson D.C., and Cirenza P.F. (2001) Expression of the insulin receptor in the retina of the goldfish. Investig. Ophthalmol. Vis. Sci. 42, 2125–2129.

    CAS  Google Scholar 

  51. Moss A.M. and Livingston J.N. (1993) Distinct beta-subunits are present in hybrid insulin-like-growth-factor-1 receptors in the central nervous system. Biochem. J. 294, 685–692.

    PubMed  CAS  Google Scholar 

  52. Efstratiadis A. (1998) Genetics of mouse growth. Int. J. Dev. Biol. 42, 955–976.

    PubMed  CAS  Google Scholar 

  53. Nakae J., Kido Y., and Accili D. (2001) Distinct and overlapping functions of insulin and IGF-I receptors. Endocr. Rev. 22, 818–835.

    Article  PubMed  CAS  Google Scholar 

  54. De Meyts P. (2002) Insulin and insulin-like growth factors: the paradox of signaling specificity. Growth Horm. IGF Res. 12, 81.

    Article  PubMed  CAS  Google Scholar 

  55. Saltiel A.R. and Pessin J.E. (2002) Insulin signaling pathways in time and space. Trends Cell Biol. 12, 65–71.

    Article  PubMed  CAS  Google Scholar 

  56. Le Borgne R., Schmidt A., Mauxion F., Griffiths G., and Hoflack B. (1993) Binding of AP-1 Golgi adaptors to membranes requires phosphorylated cytoplasmic domains of the mannose 6-phosphate/insulin-like growth factor II receptor. J. Biol. Chem. 268, 22,552–22,556.

    Google Scholar 

  57. Ludwig T., Eggenschwiler J., Fisher P., D’Ercole A.J., Davenport M.L., and Efstratiadis A. (1996) Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds. Dev. Biol. 177, 517–535.

    Article  PubMed  CAS  Google Scholar 

  58. Clairmont K.B. and Czech M.P. (1989) Chicken and Xenopus mannose 6- phosphate receptors fail to bind insulin-like growth factor II. J. Biol. Chem. 264, 16,390–16,392.

    CAS  Google Scholar 

  59. Groigno L., Bonnec G., Wolff J., Joly J., and Boujard D. (1996) Insulin-like growth factor I receptor messenger expression during oogenesis in Xenopus laevis. Endocrinology 137, 3856–3863.

    Article  PubMed  CAS  Google Scholar 

  60. Kimura K.D., Tissenbaum H.A., Liu Y., and Ruvkun G. (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946.

    Article  PubMed  CAS  Google Scholar 

  61. Leibush B.N., Lappova Y.L., Bondareva V.M., Chistyacova O.V., Gutierrez J., and Plisetskaya E.M. (1998) Insulin-family peptide-receptor interaction at the early stage of vertebrate evolution. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 121, 57–63.

    Article  PubMed  CAS  Google Scholar 

  62. Loffing-Cueni D., Schmid A.C., Graf H., and Reinecke M. (1998) IGF-I in the bony fish Cottus scorpius: cDNA, expression and differential localization in brain and islets. Mol. Cell. Endocrinol. 141, 187–194.

    Article  PubMed  CAS  Google Scholar 

  63. Ruan Y., Chen C., Cao Y., and Garofalo R.S. (1995) The Drosophila insulin receptor contains a novel carboxyl-terminal extension likely to play an important role in signal transduction. J. Biol. Chem. 270, 4236–4243.

    Article  PubMed  CAS  Google Scholar 

  64. Scavo L., Shuldiner A.R., Serrano J., Dashner R., Roth J., and de Pablo F. (1991) Genes encoding receptors for insulin and insulin-like growth factor 1 are expressed in Xenopus oocytes and embryos. Proc. Natl. Acad. Sci. USA 88, 6214–6218.

    Article  PubMed  CAS  Google Scholar 

  65. Tatar M., Kopelman A., Epstein D., Tu M.P., Yin C.M., and Garofalo R.S. (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292, 107–110.

    Article  PubMed  CAS  Google Scholar 

  66. Zhu L., Ohan N., Agazie Y., Cummings C., Farah S., and Liu X.J. (1998) Molecular cloning and characterization of Xenopus insulin-like growth factor-1 receptor: its role in mediating insulin-induced Xenopus oocyte maturation and expression during embryogenesis. Endocrinology 139, 949–954.

    Article  PubMed  CAS  Google Scholar 

  67. Collett-Solberg P.F. and Cohen P. (2000) Genetics, chemistry, and function of the IGF/IGFBP system. Endocrine 12, 121–136.

    Article  PubMed  CAS  Google Scholar 

  68. Kim H.S., Nagalla S.R., Oh Y., Wilson E., Roberts C.T., Jr., and Rosenfeld R.G. (1997) Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc. Natl. Acad. Sci. USA 94, 12,981–12,986.

    CAS  Google Scholar 

  69. Adam C.L., Gadd T.S., Findlay P.A., and Wathes D.C. (2000) IGF-I stimulation of luteinizing hormone secretion, IGF-binding proteins (IGFBPs) and expression of mRNAs for IGFs, IGF receptors and IGFBPs in the ovine pituitary gland J. Endocrinol. 166, 247–254.

    Article  PubMed  CAS  Google Scholar 

  70. Arnold P.M., Ma J.Y., Citron B.A., Zoubine M.N., and Festoff B.W. (2000) Selective developmental regulation of gene expression for insulin-like growth factor-binding proteins in mouse spinal cord. Spine 25, 1765–1770.

    Article  PubMed  CAS  Google Scholar 

  71. Ayer-le Lievre C., Stahlbom P.A., and Sara V.R. (1991) Expression of IGF-I and - II mRNA in the brain and craniofacial region of the rat fetus. Development 111, 105–115.

    PubMed  CAS  Google Scholar 

  72. Beilharz E.J., Russo V.C., Butler G., Baker N.L., Connor B., Sirimanne E.S., et al. (1998) Coordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury. Brain Res. Mol. Brain Res. 59, 119–134.

    Article  PubMed  CAS  Google Scholar 

  73. Bondy C., Werner H., Roberts C.T., Jr., and LeRoith D. (1992) Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II. Neuroscience 46, 909–923.

    Article  PubMed  CAS  Google Scholar 

  74. Bondy C. and Lee W.H. (1993) Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I gene expression during brain development. J. Neurosci. 13, 5092–5104.

    PubMed  CAS  Google Scholar 

  75. Bondy C.A., Werner H., Roberts C.T., Jr., and LeRoith D. (1990) Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. Mol. Endocrinol. 4, 1386–1398.

    PubMed  CAS  Google Scholar 

  76. Bondy C.A. (1991) Transient IGF-I gene expression during the maturation of functionally related central projection neurons. J. Neurosci. 11, 3442–3455.

    PubMed  CAS  Google Scholar 

  77. Brar A.K. and Chernausek S.D. (1993) Localization of insulin-like growth factor binding protein-4 expression in the developing and adult rat brain: analysis by in situ hybridization. J. Neurosci. Res. 35, 103–114.

    Article  PubMed  CAS  Google Scholar 

  78. Breese C.R., D’Costa A., Rollins Y.D., Adams C., Booze R.M., Sonntag W.E., et al. (1996) Expression of insulin-like growth factor-1 (IGF-1) and IGF- binding protein 2 (IGF-BP2) in the hippocampus following cytotoxic lesion of the dentate gyrus. J. Comp. Neurol. 369, 388–404.

    Article  PubMed  CAS  Google Scholar 

  79. Chernausek S.D., Murray M.A., and Cheung P.T. (1993) Expression of insulin-like growth factor binding protein-4 (IGFBP-4) by rat neural cells: comparison to other IGFBPs. Regul. Pept. 48, 123–132.

    Article  PubMed  CAS  Google Scholar 

  80. Gonzalez-Parra S., Argente J., Chowen J.A., van Kleffens M., van Neck J.W., Lindenbeigh-Kortleve D.J., et al. (2001) Gene expression of the insulin- like growth factor system during postnatal development of the rat pituitary gland J. Neuroendocrinol. 13, 86–93.

    Article  PubMed  CAS  Google Scholar 

  81. Green B.N., Jones S.B., Streck R.D., Wood T.L., Rotwein P., and Pintar J.E. (1994) Distinct expression patterns of insulin-like growth factor binding proteins 2 and 5 during fetal and postnatal development. Endocrinology 134, 954–962.

    Article  PubMed  CAS  Google Scholar 

  82. Hammarberg H., Risling M., Hokfelt T., Cullheim S., and Piehl F. (1998) Expression of insulin-like growth factors and corresponding binding proteins (IGFBP 1-6) in rat spinal cord and peripheral nerve after axonal injuries. J. Comp. Neurol. 400, 57–72.

    Article  PubMed  CAS  Google Scholar 

  83. Holley S.J., Hall S.B., and Mellon P.L. (2002) Complementary expression of IGF-II and IGFBP-5 during anterior pituitary development. Dev. Biol. 244, 319–328.

    Article  PubMed  CAS  Google Scholar 

  84. Holzenberger M., Jarvis E.D., Chong C., Grossman M., Nottebohm F., and Scharff C. (1997) Selective expression of insulin-like growth factor II in the songbird brain. J. Neurosci. 17, 6974–6987.

    PubMed  CAS  Google Scholar 

  85. Holzenberger M. and Lapointe F. (2000) Expression of insulin-like growth factor-I (IGF-I) and IGF-II in the avian brain: relationship of in situ hybridization patterns with IGF type 1 receptor expression. Int. J. Dev. Neurosci. 18, 69–82.

    Article  PubMed  CAS  Google Scholar 

  86. Lai M., Hibberd C.J., Gluckman P.D., and Seckl J.R. (2000) Reduced expression of insulin-like growth factor 1 messenger RNA in the hippocampus of aged rats. Neurosci. Lett. 288, 66–70.

    Article  PubMed  CAS  Google Scholar 

  87. Lee J.E., Pintar J., and Efstratiadis A. (1990) Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis. Development 110, 151–159.

    PubMed  CAS  Google Scholar 

  88. Lee W.H., Javedan S., and Bondy C.A. (1992) Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development. J. Neurosci. 12, 4737–4744.

    PubMed  CAS  Google Scholar 

  89. Lee W.H., Michels K.M., and Bondy C.A. (1993) Localization of insulin-like growth factor binding protein-2 messenger RNA during postnatal brain development: correlation with insulin-like growth factors I and II. Neuroscience 53, 251–265.

    Article  PubMed  CAS  Google Scholar 

  90. Leon Y., Sanz C., Frago L.M., Camarero G., Canon S., Varela-Nieto I., et al. (1999) Involvement of insulin-like growth factor-I in inner ear organogenesis and regeneration. Horm. Metab. Res. 31, 126–132.

    PubMed  CAS  Google Scholar 

  91. Logan A., Gonzalez A.M., Hill D.J., Berry M., Gregson N.A., and Baird A. (1994) Coordinated pattern of expression and localization of insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 in the adult rat brain. Endocrinology 135, 2255–2264.

    Article  PubMed  CAS  Google Scholar 

  92. Naeve G.S., Vana A.M., Eggold J.R., Verge G., Ling N., and Foster A.C. (2000) Expression of rat insulin-like growth factor binding protein-6 in the brain, spinal cord, and sensory ganglia. Brain Res. Mol. Brain Res. 75, 185–197.

    Article  PubMed  CAS  Google Scholar 

  93. Niblock M.M., Brunso-Bechtold J.K., Lynch C.D., Ingram R.L., McShane T., and Sonntag W.E. (1998) Distribution and levels of insulin-like growth factor I mRNA across the life span in the Brown Norway x Fischer 344 rat brain. Brain Res. 804, 79–86.

    Article  PubMed  CAS  Google Scholar 

  94. Petersson S., Sandberg Nordqvist A., Schalling M., and Lavebratt C. (1999) The megencephaly mouse has disturbances in the insulin-like growth factor (IGF) system. Brain Res. Mol. Brain Res. 72, 80–88.

    Article  PubMed  CAS  Google Scholar 

  95. Russo V.C., Edmondson S.R., Mercuri F.A., Buchanan C.R., and Werther G.A. (1994) Identification, localization, and regulation of insulin-like growth factor binding proteins and their messenger ribonucleic acids in the newborn rat olfactory bulb. Endocrinology 135, 1437–1446.

    Article  PubMed  CAS  Google Scholar 

  96. Sandberg Nordqvist A.C., von Holst H., Holmin S., Sara V.R., Bellander B.M., and Schalling M. (1996) Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion. Brain Res. Mol. Brain Res. 38, 285–293.

    Article  PubMed  CAS  Google Scholar 

  97. Sonntag W.E., Lynch C.D., Bennett S.A., Khan A.S., Thornton P.L., Cooney P.T., et al. (1999) Alterations in insulin-like growth factor-1 gene and protein expression and type 1 insulin-like growth factor receptors in the brains of ageing rats. Neuroscience 88, 269–279.

    Article  PubMed  CAS  Google Scholar 

  98. Stenvers K.L., Zimmermann E.M., Gallagher M., and Lund P.K. (1994) Expression of insulin-like growth factor binding protein-4 and -5 mRNAs in adult rat forebrain. J. Comp. Neurol. 339, 91–105.

    Article  PubMed  CAS  Google Scholar 

  99. Stenvers K.L., Lund P.K., and Gallagher M. (1996) Increased expression of type 1 insulin-like growth factor receptor messenger RNA in rat hippocampal formation is associated with aging and behavioral impairment. Neuroscience 72, 505–518.

    Article  PubMed  CAS  Google Scholar 

  100. Streck R.D. and Pintar J.E. (1992) The embryonic pattern of rat insulin-like growth factor-I gene expression suggests a role in induction and early growth of the liver. Endocrinology 131, 2030–2032.

    Article  PubMed  CAS  Google Scholar 

  101. Stylianopoulou F., Efstratiadis A., Herbert J., and Pintar J. (1988) Pattern of the insulin-like growth factor II gene expression during rat embryogenesis. Development 103, 497–506.

    PubMed  CAS  Google Scholar 

  102. Torres-Aleman I., Pons S., and Arevalo M.A. (1994) The insulin-like growth factor I system in the rat cerebellum: developmental regulation and role in neuronal survival and differentiation. J. Neurosci Res. 39, 117–126.

    Article  PubMed  CAS  Google Scholar 

  103. Walter H.J., Berry M., Hill D.J., and Logan A. (1997) Spatial and temporal changes in the insulin-like growth factor (IGF) axis indicate autocrine/paracrine actions of IGF-1 within wounds of the rat brain. Endocrinology 138, 3024–3034.

    Article  PubMed  CAS  Google Scholar 

  104. Walter H.J., Berry M., Hill D.J., Cwyfan-Hughes S., Holly J.M., and Logan A. (1999) Distinct sites of insulin-like growth factor (IGF)-II expression and localization in lesioned rat brain: possible roles of IGF binding proteins (IGFBPs) in the mediation of IGF-II activity. Endocrinology 140, 520–532.

    Article  PubMed  CAS  Google Scholar 

  105. Wood T.L., Brown A.L., Rechler M.M., and Pintar J.E. (1990) The expression pattern of an insulin-like growth factor (IGF)-binding protein gene is distinct from IGF-II in the midgestational rat embryo. Mol. Endocrinol. 4, 1257–1263.

    PubMed  CAS  Google Scholar 

  106. Wood T.L., Streck R.D., and Pintar J.E. (1992) Expression of the IGFBP-2 gene in post-implantation rat embryos. Development 114, 59–66.

    PubMed  CAS  Google Scholar 

  107. Ye P. and D’Ercole J. (1998) Insulin-like growth factor I (IGF-I) regulates IGF binding protein-5 gene expression in the brain. Endocrinology 139, 65–71.

    Article  PubMed  CAS  Google Scholar 

  108. Zhou X., Herman J.P., and Paden C.M. (1997) Expression of insulin-like growth factor binding protein-2 during postnatal development of the rat neurointermediate pituitary. Neuroendocrinology 66, 17–27.

    PubMed  CAS  Google Scholar 

  109. Schoen T.J., Bondy C.A., Zhou J., Dhawan R., Mazuruk K., Arnold D.R., et al. (1995) Differential temporal and spatial expression of insulin-like growth factor binding protein-2 in developing chick ocular tissues. Investig. Ophthalmol. Vis. Sci. 36, 2652–2662.

    CAS  Google Scholar 

  110. Bartlett W.P., Li X.S., Williams M., and Benkovic S. (1991) Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development. Dev. Biol. 147, 239–250.

    Article  PubMed  CAS  Google Scholar 

  111. Camarero G., Avendano C., Fernandez-Moreno C., Villar A., Contreras J., de Pablo F., et al. (2001) Delayed inner ear maturation and neuronal loss in postnatal lgf-1-deficient mice. J. Neurosci. 21, 7630–7641.

    PubMed  CAS  Google Scholar 

  112. Diaz B., Serna J., de Pablo F., and de la Rosa E.J. (2000) In vivo regulation of cell death by embryonic (pro)insulin and the insulin receptor during early retinal neurogenesis. Development 127, 1641–1649.

    PubMed  CAS  Google Scholar 

  113. Alarcon C., Serna J., Perez-Villamil B., and de Pablo F. (1998) Synthesis and differentially regulated processing of proinsulin in developing chick pancreas, liver and neuroretina. FEBS Lett. 436, 361–366.

    Article  PubMed  CAS  Google Scholar 

  114. Marks J.L., Porte D., Jr., and Baskin D.G. (1991) Localization of type I insulin-like growth factor receptor messenger RNA in the adult rat brain by in situ hybridization. Mol. Endocrinol. 5, 1158–1168.

    PubMed  CAS  Google Scholar 

  115. Zhang W., Ghetti B., and Lee W.H. (1997) Decreased IGF-1 gene expression during the apoptosis of Purkinje cells in pcd mice. Brain Res. Dev. Brain Res. 98, 164–176.

    Article  PubMed  CAS  Google Scholar 

  116. Elmlinger M.W., Deininger M.H., Schuett B.S., Meyermann R., Duffner F., Grote E.H., et al. (2001) In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology 142, 1652–1658.

    Article  PubMed  CAS  Google Scholar 

  117. Unterman T.G., Glick R.P., Waites G.T., and Bell S.C. (1991) Production of insulin-like growth factor-binding proteins by human central nervous system tumors. Cancer Res. 51, 3030–3036.

    PubMed  CAS  Google Scholar 

  118. Zumkeller W. and Westphal M. (2001) The IGF/IGFBP system in CNS malignancy. Mol. Pathol. 54, 227–229.

    Article  PubMed  CAS  Google Scholar 

  119. Dore S., Kar S., Rowe W., and Quirion R. (1997) Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats. Neuroscience 80, 1033–1040.

    Article  PubMed  CAS  Google Scholar 

  120. Eriksson P.S., Perfilieva E., Bjork-Eriksson T., Alborn A.M., Nordborg C., Peterson D.A., et al. (1998) Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313–1317.

    Article  PubMed  CAS  Google Scholar 

  121. Syroid D.E., Zorick T.S., Arbet-Engels C., Kilpatrick T.J., Eckhart W., and Lemke G. (1999) A role for insulin-like growth factor-I in the regulation of Schwann cell survival. J. Neurosci. 19, 2059–2068.

    PubMed  CAS  Google Scholar 

  122. Anderson M.F., Aberg M.A., Nilsson M., and Eriksson P.S. (2002) Insulin-like growth factor-I and neurogenesis in the adult mammalian brain. Brain Res. Dev. Brain Res. 134, 115–122.

    Article  PubMed  CAS  Google Scholar 

  123. Alarcon C., Morales A.V., Pimentel B., Serna J., and de Pablo F. (1998) (Pro)insulin and insulin-like growth factor I complementary expression and roles in early development. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 121, 13–17.

    Article  PubMed  CAS  Google Scholar 

  124. de la Rosa E.J., Bondy C.A., Hernandez-Sanchez C., Wu X., Zhou J., Lopez-Carranza A., et al. (1994) Insulin and insulin-like growth factor system components gene expression in the chicken retina from early neurogenesis until late development and their effect on neuroepithelial cells. Eur. J. Neurosci. 6, 1801–1810.

    Article  PubMed  Google Scholar 

  125. de Pablo F., Roth J., Hernandez E., and Pruss R.M. (1982) Insulin is present in chicken eggs and early chick embryos. Endocrinology 111, 1909–1916.

    Article  PubMed  Google Scholar 

  126. Deltour L., Leduque P., Blume N., Madsen O., Dubois P., Jami J., et al. (1993) Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo. Proc. Natl. Acad. Sci. USA 90, 527–531.

    Article  PubMed  CAS  Google Scholar 

  127. Devaskar S.U., Giddings S.J., Rajakumar P.A., Carnaghi L.R., Menon R.K., and Zahm D.S. (1994) Insulin gene expression and insulin synthesis in mammalian neuronal cells. J. Biol. Chem. 269, 8445–8454.

    PubMed  CAS  Google Scholar 

  128. Diaz B., Pimentel B., de Pablo F., and de la Rosa E.J. (1999) Apoptotic cell death of proliferating neuroepithelial cells in the embryonic retina is prevented by insulin. Eur. J. Neurosci. 11, 1624–1632.

    Article  PubMed  CAS  Google Scholar 

  129. Morales A.V., Serna J., Alarcon C., de la Rosa E.J., and de Pablo F. (1997) Role of prepancreatic (pro)insulin and the insulin receptor in prevention of embryonic apoptosis. Endocrinology 138, 3967–3975.

    Article  PubMed  CAS  Google Scholar 

  130. Shuldiner A.R., de Pablo F., Moore C.A., and Roth J. (1991) Two nonallelic insulin genes in Xenopus laevis are expressed differentially during neurulation in prepancreatic embryos. Proc. Natl. Acad. Sci. USA 88, 7679–7683.

    Article  PubMed  CAS  Google Scholar 

  131. de la Rosa E.J., Vega-Nuñez E., Morales A.V., Serna J., Rubio E., and de Pablo F. (1998) Modulation of the chaperone heat shock cognate 70 by embryonic (pro)insulin correlates with prevention of apoptosis. Proc. Natl. Acad. Sci. USA 95, 9950–9955.

    Article  PubMed  Google Scholar 

  132. Couce M.E., Weatherington A.J., and McGinty J.F. (1992) Expression of insulin-like growth factor-II (IGF-II) and IGF-II/mannose-6-phosphate receptor in the rat hippocampus: an in situ hybridization and immunocytochemical study. Endocrinology 131, 1636–1642.

    Article  PubMed  CAS  Google Scholar 

  133. Hawkes C. and Kar S. (2002) Insulin-like growth factor-II/Mannose-6-phosphate receptor in the spinal cord and dorsal root ganglia of the adult rat. Eur. J. Neurosci. 15, 33–39.

    Article  PubMed  CAS  Google Scholar 

  134. Matzner U., von Figura K., and Pohlmann R. (1992) Expression of the two mannose 6-phosphate receptors is spatially and temporally different during mouse embryogenesis. Development 114, 965–972.

    PubMed  CAS  Google Scholar 

  135. Lichtenwalner R.J., Forbes M.E., Bennett S.A., Lynch C.D., Sonntag W.E., and Riddle D.R (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107, 603–613.

    Article  PubMed  CAS  Google Scholar 

  136. Torres-Aleman I. (2000) Serum growth factors and neuroprotective surveillance: focus on IGF-1. Mol. Neurobiol. 21, 153–160.

    Article  PubMed  CAS  Google Scholar 

  137. Carro E., Trejo J.L., Gomez-Isla T., LeRoith D., and Torres-Aleman I. (2002) Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat. Med. 8, 1390–1397.

    Article  PubMed  CAS  Google Scholar 

  138. Linseman D.A., McClure M.L., Bouchard R.J., Laessig T.A., Ahmadi F.A., and Heidenreich K.A. (2002) Suppression of death receptor signaling in cerebellar Purkinje neurons protects neighboring granule neurons from apoptosis via an insulin-like growth factor I-dependent mechanism. J. Biol. Chem. 277, 24,546–24,553.

    Article  CAS  Google Scholar 

  139. Pu S.F., Zhuang H.X., and Ishii D.N. (1995) Differential spatio-temporal expression of the insulin-like growth factor genes in regenerating sciatic nerve. Brain Res. Mol. Brain Res. 34, 18–28.

    Article  PubMed  CAS  Google Scholar 

  140. Pu S.F., Zhuang H.X., Marsh D.J., and Ishii D.N. (1999) Insulin-like growth factor-II increases and IGF is required for postnatal rat spinal motoneuron survival following sciatic nerve axotomy. J. Neurosci. Res. 55, 9–16.

    Article  PubMed  CAS  Google Scholar 

  141. Sondell M., Fex-Svenningsen A., and Kanje M. (1997) The insulin-like growth factors I and II stimulate proliferation of different types of Schwann cells. Neuroreport 8, 2871–2876.

    Article  PubMed  CAS  Google Scholar 

  142. Kar S., Seto D., Dore S., Chabot J.G., and Quirion R. (1997) Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation. Neuroscience 80, 1041–1055.

    Article  PubMed  CAS  Google Scholar 

  143. Mewar R. and McMorris F.A. (1997) Expression of insulin-lik growth factor-binding protein messenger RNAs in developing rat oligodendrocytes and astrocytes. J. Neurosci. Res. 50, 721–728.

    Article  PubMed  CAS  Google Scholar 

  144. Wilkins A., Chandran S., and Compston A. (2001) A role for oligodendrocyte-derived IGF-1 in trophic support of cortical neurons. Glia 36, 48–57.

    Article  PubMed  CAS  Google Scholar 

  145. Funk B., Kessler U., Eisenmenger W., Hansmann A., Kolb H.J., and Kiess W. (1992) The expression of insulin-like growth factor binding proteins is tissue specific during human fetal life and early infancy. Acta Endocrinol. (Copenh) 127, 107–114.

    CAS  Google Scholar 

  146. Cheng H.L., Sullivan K.A., and Feldman E.L. (1996) Immunohistochemical localization of insulin-like growth factor binding protein-5 in the developing rat nervous system. Brain Res. Dev. Brain Res. 92, 211–218.

    Article  PubMed  CAS  Google Scholar 

  147. Aberg M.A., Aberg N.D., Hedbacker H., Oscarsson J., and Eriksson P.S. (2000) Peripheral infusion of IGF-I selectivity induces neurogenesis in the adult rat hippocampus. J. Neurosci. 20, 2896–2903.

    PubMed  CAS  Google Scholar 

  148. Arsenijevic Y., Weiss S., Schneider B., and Aebischer P. (2001) Insulin-like growth factor-I is necessary for neural stem cell proliferation and demonstrates distinct actions of epidermal growth factor and fibroblast growth factor-2 J. Neurosci. 21, 7194–7202.

    PubMed  CAS  Google Scholar 

  149. Bitar M.S., Francis I.M., and Pilcher C.W. (2000) Insulin-like growth factor 1-induced alterations in lumbospinal monoamine dynamics. Horm. Metab. Res. 32, 207–215.

    PubMed  CAS  Google Scholar 

  150. Blair L.A. and Marshall J. (1997) IGF-1 modulates N and L calcium channels in a PI 3-kinase-dependent manner. Neuron 19, 421–429.

    Article  PubMed  CAS  Google Scholar 

  151. Boucher S.E. and Hitchcock P.F. (1998) Insulin-related growth factors stimulate proliferation of retinal progenitors in the goldfish. J. Comp. Neurol. 394, 386–394.

    Article  PubMed  CAS  Google Scholar 

  152. Brooker G.J., Kalloniatis M., Russo V.C., Murphy M., Werther G.A., and Bartlett P.F. (2000) Endogenous IGF-1 regulates the neuronal differentiation of adult stem cells. J. Neurosci. Res. 59, 332–341.

    Article  PubMed  CAS  Google Scholar 

  153. Camarero G., Villar M., Contreras J., Fernandez-Moreno C., Pichel J., Avendano C., and Varela-Nieto I. (2002) Cochlear abnormalities in insulin-like growth factor-1 mouse mutants. Hear. Res. 170, 2.

    Article  PubMed  CAS  Google Scholar 

  154. Campana W.M., Darin S.J., and O’Brien J.S. (1999) Phosphatidylinositol 3-kinase and Akt protein kinase mediate IGF-I- and prosaptide-induced survival in Schwann cells. J. Neurosci. Res. 57, 332–341.

    Article  PubMed  CAS  Google Scholar 

  155. Caplan J., Tiangco D.A., and Terzis J.K. (1999) Effects of IGF-II in a new end-to-side model. J. Reconstr. Microsurg. 15, 351–358.

    PubMed  CAS  Google Scholar 

  156. Cardona-Gomez G.P., Trejo J.L., Fernandez A.M., and Garcia-Segura L.M. (2000) Estrogen receptors and insulin-like growth factor-I receptors mediate estrogen-dependent synaptic plasticity. Neuroreport 11, 1735–1738.

    Article  PubMed  CAS  Google Scholar 

  157. Carson M.J., Behringer R.R., Brinster R.L., and McMorris F.A. (1993) Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron 10, 729–740.

    Article  PubMed  CAS  Google Scholar 

  158. Castro-Alamancos M.A. and Torres-Aleman I. (1994) Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide. Proc. Natl. Acad. Sci. USA 91, 10,203–10,207.

    Article  CAS  Google Scholar 

  159. Cheng H.L., Steinway M.L., Xin X., and Feldman E.L. (2001) Insulin-like growth factor-I and Bcl-X(L) inhibit c-jun N-terminal kinase activation and rescue Schwann cells from apoptosis. J. Neurochem. 76, 935–943.

    Article  PubMed  CAS  Google Scholar 

  160. Cheng H.L. and Feldman E.L. (1997) Insulin-like growth factor-I (IGF-I) and IGF binding protein-5 in Schwann cell differentiation. J. Cell Physiol. 171, 161–167.

    Article  PubMed  CAS  Google Scholar 

  161. Cheng H.L., Shy M., and Feldman E.L. (1999) Regulation of insulin-like growth factor-binding protein-5 expression during Schwann cell differentiation. Endocrinology 140, 4478–4485.

    Article  PubMed  CAS  Google Scholar 

  162. Chik C.L., Li B., Karpinski E., and Ho A.K. (1997) Insulin and insulin-like growth factor-I inhibit the L-type calcium channel current in rat pinealocytes. Endocrinology 138, 2033–2042.

    Article  PubMed  CAS  Google Scholar 

  163. Cho K.H., Kim M.W., and Kim S.U. (1997) Tissue culture model of Krabbe’s disease: psychosine cytotoxicity in rat oligodendrocyte culture. Dev. Neurosci. 19, 321–327.

    PubMed  CAS  Google Scholar 

  164. Chrysis D., Calikoglu A.S., Ye P., and D’Ercole A.J. (2001) Insulin-like growth factor-I overexpression attenuates cerebellar apoptosis by altering the expression of Bcl family proteins in a developmentally specific manner. J. Neurosci. 21, 1481–1489.

    PubMed  CAS  Google Scholar 

  165. Cui H. and Bulleit R.F. (1998) Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors. Brain Res. Dev. Brain Res. 106, 129–135.

    Article  PubMed  CAS  Google Scholar 

  166. D’Costa A.P., Prevette D.M., Houenou L.J., Wang S., Zackenfels K., Rohrer H., et al. (1998) Mechanisms of insulin-like growth factor regulation of programmed cell death of developing avian motoneurons. J. Neurobiol. 36, 379–394.

    Article  PubMed  CAS  Google Scholar 

  167. D’Mello S.R., Galli C., Ciotti T., and Calissano P. (1993) Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor 1 and cAMP. Proc. Natl. Acad. Sci. USA 90, 10,989–10,993.

    Article  CAS  Google Scholar 

  168. Delaney C.L., Russell J.W., Cheng H.L., and Feldman E.L. (2001) Insulin-like growth factor-I and over-expression of Bcl-xL prevent glucose-mediated apoptosis in Schwann cells. J. Neuropathol. Exp. Neurol. 60, 147–160.

    PubMed  CAS  Google Scholar 

  169. Delaney C.L., Cheng H.L., and Feldman E.L. (1999) Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwann cells. J. Neurobiol. 41, 540–548.

    Article  PubMed  CAS  Google Scholar 

  170. Dentremont K.D., Ye P., D’Ercole A.J., and O’Kusky J.R. (1999) Increased insulin-like growth factor-I (IGF-I) expression during early postnatal development differentially increases neuron number and growth in medullary nuclei of the mouse. Brain Res. Dev. Brain Res. 114, 135–141.

    Article  PubMed  CAS  Google Scholar 

  171. Edbladh M., Fex-Svenningsen A., Ekstrom P.A., and Edstrom A. (1994) Insulin and IGF-II, but not IGF-I, stimulate the in vitro regeneration of adult frog sciatic sensory axons. Brain Res. 641, 76–82.

    Article  PubMed  CAS  Google Scholar 

  172. Engele J. (1998) Changing responsiveness of developing midbrain dopaminergic neurons for extracellular growth factors. J. Neurosci. Res. 51, 508–516.

    Article  PubMed  CAS  Google Scholar 

  173. Eustache I., Seyfritz N., and Gueritaud J.P. (1994) Effects of insulin-like growth factors on organotypic cocultures of embryonic rat brain-stem slices and skeletal muscle fibers. Brain Res. Dev. Brain Res. 81, 284–292.

    Article  PubMed  CAS  Google Scholar 

  174. Fernandez-Galaz M.C., Naftolin F., and Garcia-Segura L.M. (1999) Phasic synaptic remodeling of the rat arcuate nucleus during the estrous cycle depends on insulin-like growth factor-I receptor activation. J. Neurosci. Res. 55, 286–292.

    Article  PubMed  CAS  Google Scholar 

  175. Frade J.M., Marti E., Bovolenta P., Rodriguez-Pena M.A., Perez-Garcia D., Rohrer H., et al. (1996) Insulin-like growth factor-I stimulates neurogenesis in chick retina by regulating expression of the alpha 6 integrin subunit. Development 122, 2497–2506.

    PubMed  CAS  Google Scholar 

  176. Gardoni F., Kamal A., Bellone C., Biessels G.J., Ramakers G.M., Cattabeni F., et al. (2002) Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats. J. Neurochem. 80, 438–447.

    Article  PubMed  CAS  Google Scholar 

  177. Gleichmann M., Weller M., and Schulz J.B. (2000) Insulin-like growth factor-1-mediated protection from neuronal apoptosis is linked to phosphorylation of the pro-apoptotic protein BAD but not to inhibition of cytochrome c translocation in rat cerebellar neurons. Neurosci. Lett. 282, 69–72.

    Article  PubMed  CAS  Google Scholar 

  178. Gonzalez d.l., V, Buno W., Pons S., Garcia-Calderat M.S., Garcia-Galloway E., and Torres-Aleman I. (2001) Insulin-like growth factor I potentiates kainate receptors through a phosphatidylinositol 3-kinase dependent pathway. Neuroreport 12, 1293–1296.

    Article  Google Scholar 

  179. Guan J., Miller O.T., Waugh K.M., McCarthy D.C., and Gluckman P.D. (2001) Insulin-like growth factor-1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats. Neuroscience 105, 299–306.

    Article  PubMed  CAS  Google Scholar 

  180. Gunn-Moore F.J., Williams A.G., Toms N.J., and Tavare J.M. (1997) Activation of mitogen-activated protein kinase and p70S6 kinase is not correlated with cerebellar granule cell survival. Biochem. J. 324, 365–369.

    PubMed  CAS  Google Scholar 

  181. Hausman R.E., Sagar G.D., and Shah B.H. (1991) Initial cholinergic differentiation in embryonic chick retina is responsive to insulin and cell-cell interactions. Brain Res. Dev. Brain Res. 59, 31–37.

    Article  PubMed  CAS  Google Scholar 

  182. Hernandez-Sanchez C., Lopez-Carranza A., Alarcon C., de la Rosa E.J., and de Pablo F. (1995) Autocrine/paracrine role of insulin-related growth factors in neurogenesis: local expression and effects on cell proliferation and differentiation in retina. Proc. Natl. Acad. Sci. USA 92, 9834–9838.

    Article  PubMed  CAS  Google Scholar 

  183. Janiga T.A., Rind H.B., and von Bartheld C.S. (2000) Differential effects of the trophic factors BDNF, NT-4, GDNF, and IGF-I on the isthmooptic nucleus in chick embryos. J. Neurobiol. 43, 289–303.

    Article  PubMed  CAS  Google Scholar 

  184. Jiang F., Frederick T.J., and Wood T.L. (2001) IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle. Dev. Biol. 232, 414–423.

    Article  PubMed  CAS  Google Scholar 

  185. Kelsch W., Hormuzdi S., Straube E., Lewen A., Monyer H., and Misgeld U. (2001) Insulin-like growth factor 1 and a cytosolic tyrosine kinase activate chloride outward transport during maturation of hippocampal neurons. J. Neurosci. 21, 8339–8347.

    PubMed  CAS  Google Scholar 

  186. Kermer P., Ankerhold R., Klocker N., Krajewski S., Reed J.C., and Bahr M. (2000) Caspase-9: involvement in secondary death of axotomized rat retinal ganglion cells in vivo. Brain Res. Mol. Brain Res. 85, 144–150.

    Article  PubMed  CAS  Google Scholar 

  187. Kermer P., Klocker N., Labes M., and Bahr M. (2000) Insulin-like growth factor-I protects axotomized rat retinal ganglion cells from secondary death via PI3-K-dependent Akt phosphorylation and inhibition of caspase-3 In vivo. J. Neurosci. 20, 2–8.

    PubMed  CAS  Google Scholar 

  188. Leon Y., Vazquez E., Sanz C., Vega J.A., Mato J.M., Giraldez F., et al. (1995) Insulin-like growth factor-1 regulates cell proliferation in the developing inner ear, activating glycosyl-phosphatidylinositol hydrolysis and Fos expression. Endocrinology 136, 3494–3503.

    Article  PubMed  CAS  Google Scholar 

  189. Leski M.L., Valentine S.L., Baer J.D., and Coyle J.T. (2000) Insulin-like growth factor I prevents the development of sensitivity to kainate neurotoxicity in cerebellar granule cells. J. Neurochem. 75, 1548–1556.

    Article  PubMed  CAS  Google Scholar 

  190. Lin X. and Bulleit R.F. (1997) Insulin-like growth factor I (IGF-I) is a critical trophic factor for developing cerebellar granule cells. Brain Res. Dev. Brain Res. 99, 234–242.

    Article  PubMed  CAS  Google Scholar 

  191. Lindholm D., Carroll P., Tzimagiogis G., and Thoenen H. (1996) Autocrine-paracrine regulation of hippocampal neuron survival by IGF-1 and the neurotrophins BDNF, NT-3 and NT-4. Eur. J. Neurosci. 8, 1452–1460.

    Article  PubMed  CAS  Google Scholar 

  192. Lu N., Black I.B., and DiCicco-Bloom E. (1996) A paradigm for distinguishing the roles of mitogenesis and trophism in neuronal precursor proliferation. Brain Res. Dev. Brain Res. 94, 31–36.

    Article  PubMed  CAS  Google Scholar 

  193. Mack A.F. and Fernald R.D. (1993) Regulation of cell division and rod differentiation in the teleost retina. Brain Res. Dev. Brain Res. 76, 183–187.

    Article  PubMed  CAS  Google Scholar 

  194. Man H.Y., Lin J.W., Ju W.H., Ahmadian G., Liu L., Becker L.E., et al. (2000) Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron 25, 649–662.

    Article  PubMed  CAS  Google Scholar 

  195. Mathonnet M., Cubertafond P., Gainant A., and Ayer-Le L.C. (2001) The avian peripheral olfactory system: model for study of apoptosis and cellular regeneration. Ann. Chir. 126, 888–895.

    Article  PubMed  CAS  Google Scholar 

  196. Matsuda T., Murata Y., Tanaka K., Hosoi R., Hayashi M., Tamada K., et al. (1996) Involvement of Na+,K(+)ATPase in the mitogenic effect of insulin-like growth factor-1 on cultured rat astrocytes. J. Neurochem. 66, 511–516.

    PubMed  CAS  Google Scholar 

  197. Matsuzaki H., Tamatani M., Mitsuda N., Namikawa K., Kiyama H., Miyake S., et al. (1999) Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons. J. Neurochem. 73, 2037–2046.

    PubMed  CAS  Google Scholar 

  198. Meier C., Parmantier E., Brennan A., Mirsky R., and Jessen K.R. (1999) Developing Schwann cells acquire the ability to survive without axons by establishing an autocrine circuit involving insulin-like growth factor, neurotrophin-3, and platelet-derived growth factor-BB. J. Neurosci. 19, 3847–3859.

    PubMed  CAS  Google Scholar 

  199. Miller B.H. and Gore A.C. (2001) Alterations in hypothalamic insulin-like growth factor-I and its associations with gonadotropin releasing hormone neurones during reproductive development and ageing. J. Neuroendocrinol. 13, 728–736.

    Article  PubMed  CAS  Google Scholar 

  200. Miller T.M., Tansey M.G., Johnson E.M.J., and Creedon D.J. (1997) Inhibition of phosphatidylinositol 3-kinase activity blocks depolarization- and insulin-like growth factor I-mediated survival of cerebellar granule cells. J. Biol. Chem. 272, 9847–9853.

    Article  PubMed  CAS  Google Scholar 

  201. Mora A., Gonzalez-Polo R.A., Fuentes J.M., Soler G., and Centeno F. (1999) Different mechanisms of protection against apoptosis by valproate and Li+. Eur. J. Biochem. 266, 886–891.

    Article  PubMed  CAS  Google Scholar 

  202. Nakao Y., Otani H., Yamamura T., Hattori R., Osako M., and Imamura H. (2001) Insulin-like growth factor 1 prevents neuronal cell death and paraplegia in the rabbit model of spinal cord ischemia. J. Thorac. Cardiovasc. Surg. 122, 136–143.

    Article  PubMed  CAS  Google Scholar 

  203. Neff N.T., Prevette D., Houenou L.J., Lewis M.E., Glicksman M.A., Yin Q.W., et al. (1993) Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival. J. Neurobiol. 24, 1578–1588.

    Article  PubMed  CAS  Google Scholar 

  204. Ni W., Rajkumar K., Nagy J.I., and Murphy L.J. (1997) Impaired brain development and reduced astrocyte response to injury in transgenic mice expressing IGF binding protein-1. Brain Res. 769, 97–107.

    Article  PubMed  CAS  Google Scholar 

  205. Niblock M.M., Brunso-Bechtold J.K., Lynch C.D., Ingram R.L., McShane T., and Sonntag W.E. (1998) Distribution and levels of insulin-like growth factor I mRNA across the life span in the Brown Norway x Fischer 344 rat brain. Brain Res 804, 79–86.

    Article  PubMed  CAS  Google Scholar 

  206. Nicholas R.S., Stevens S., Wing M.G., and Compston D.A. (2002) Microglia-derived IGF-2 prevents TNF alpha induced death of mature oligodendrocytes in vitro. J. Neuroimmunol. 124, 36–44.

    Article  PubMed  CAS  Google Scholar 

  207. Nieto-Bona M.P., Garcia-Segura L.M., and Torres-Aleman I. (1997) Transynaptic modulation by insulin-like growth factor 1 of dendritic spines in Purkinje cells. Int. J. Dev. Neurosci. 15, 749–754.

    Article  PubMed  CAS  Google Scholar 

  208. O’Kusky J.R., Ye P., and D’Ercole (2000) A.J. Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. J. Neurosci. 20, 8435–8442.

    PubMed  CAS  Google Scholar 

  209. Passafaro M., Piech V., and Sheng M. (2001) Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat. Neurosci. 4, 917–926.

    Article  PubMed  CAS  Google Scholar 

  210. Pixley S.K., Dangoria N.S., Odoms K.K., and Hastings L. (1998) Effects of insulin-like growth factor 1 on olfactory neurogenesis in vivo and in vitro. Ann. NY Acad. Sci. 855, 244–247.

    Article  PubMed  CAS  Google Scholar 

  211. Politi L.E., Rotstein N.P., Salvador G., Giusto N.M., and Insua M.F. (2001) Insulin-like growth factor-I is a potential trophic factor for amacrine cells. J. Neurochem. 76, 1199–1211.

    Article  PubMed  CAS  Google Scholar 

  212. Pomerance M., Gavaret J.M., Breton M., and Pierre M. (1995) Effects of growth factors on phosphatidylinositol-3 kinase in astroglial cells. J. Neurosci. Res. 40, 737–746.

    Article  PubMed  CAS  Google Scholar 

  213. Rind H.B. and von Bartheld C.S. (2002) Target-derived cardiotrophin-1 and insulin-like growth factor-I promote neurite growth and survival of developing oculomotor neurons. Mol. Cell. Neurosci. 19, 58–71.

    Article  PubMed  CAS  Google Scholar 

  214. Russell J.W., Windebank A.J., Schenone A., and Feldman E.L. (1998) Insulin-like growth factor-I prevents apoptosis in neurons after nerve growth factor withdrawal. J. Neurobiol. 36, 455–467.

    Article  PubMed  CAS  Google Scholar 

  215. Russell J.W. and Feldman E.L. (1999) Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose. Horm. Metab. Res. 31, 90–96.

    Article  PubMed  CAS  Google Scholar 

  216. Ryu B.R., Ko H.W., Jou I., Noh J.S., and Gwag B.J. (1999) Phosphatidylinositol 3-kinase-mediated regulation of neuronal apoptosis and necrosis by insulin and IGF-I. J. Neurobiol. 39, 536–546.

    Article  PubMed  CAS  Google Scholar 

  217. Salceda R. (1999) Insulin-stimulated taurine uptake in rat retina and retinal pigment epithelium. Neurochem. Int. 35, 301–306.

    Article  PubMed  CAS  Google Scholar 

  218. Satoh J. and Kim S.U. (1994) Proliferation and differentiation of fetal human oligodendrocytes in culture. J. Neurosci. Res. 39, 260–272.

    Article  PubMed  CAS  Google Scholar 

  219. Schechter R., Yanovitch T., Abboud M., Johnson G., III, and Gaskins J. (1998) Effects of brain endogenous insulin on neurofilament and MAPK in fetal rat neuron cell cultures. Brain Res. 19, 270–278.

    Article  Google Scholar 

  220. Schechter R. and Abboud M. (2001) Neuronal synthesized insulin roles on neural differentiation within fetal rat neuron cell cultures. Brain Res. Dev. Brain Res. 127, 41–49.

    Article  PubMed  CAS  Google Scholar 

  221. Shah B.H. and Hausman R.E. (1993) Effects of cell signaling on the development of GABA receptors in chick retina neurons. Neurochem. Res. 18, 957–964.

    Article  PubMed  CAS  Google Scholar 

  222. Shindler K.S., Yunker A.M., Cahn R., Zha J., Korsmeyer S.J., and Roth K.A. (1998) Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro. Cell Death Differ. 5, 901–910.

    Article  PubMed  CAS  Google Scholar 

  223. Shiotani A., O’Malley B.W., Jr., Coleman M.E., and Flint P.W. (1999) Human insulin-like growth factor 1 gene transfer into paralyzed rat larynx: single vs multiple injection. Arch. Otolaryngol. Head Neck Surg. 125, 555–560.

    PubMed  CAS  Google Scholar 

  224. Stella S.L.J., Bryson E.J., and Thoreson W.B. (2001) Insulin inhibits voltage-dependent calcium influx into rod photoreceptors. Neuroreport 12, 947–951.

    Article  PubMed  CAS  Google Scholar 

  225. Stewart H.J., Bradke F., Tabernero A., Morrell D., Jessen K.R., and Mirsky R. (1996) Regulation of rat Schwann cell Po expression and DNA synthesis by insulin-like growth factors in vitro. Eur. J. Neurosci. 8, 553–564.

    Article  PubMed  CAS  Google Scholar 

  226. Svenningsen A.F. and Kanje M. (1996) Insulin and the insulin-like growth factors I and II are mitogenic to cultured rat sciatic nerve segments and stimulate [3H]thymidine incorporation through their respective receptors. Glia 18, 68–72.

    Article  PubMed  CAS  Google Scholar 

  227. Tagami M., Ikeda K., Nara Y., Fujino H., Kubota A., Numano F., et al. (1997) Insulin-like growth factor-1 attenuates apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats. Lab. Investig. 76, 613–617.

    PubMed  CAS  Google Scholar 

  228. Tagami M., Yamagata K., Nara Y., Fujino H., Kubota A., Numano F., et al. (1997) Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats. Lab. Investig. 76, 603–612.

    PubMed  CAS  Google Scholar 

  229. Takadera T., Matsuda I., and Ohyashiki T. (1999) Apoptotic cell death and caspase-3 activation induced by N-methyl-D-aspartate receptor antagonists and their prevention by insulin-like growth factor I. J. Neurochem. 73, 548–556.

    Article  PubMed  CAS  Google Scholar 

  230. Tamatani M., Ogawa S., and Tohyama M. (1998) Roles of Bcl-2 and caspases in hypoxia-induced neuronal cell death: a possible neuroprotective mechanism of peptide growth factors. Brain Res. Mol. Brain Res. 58, 27–39.

    Article  PubMed  CAS  Google Scholar 

  231. Tanabe H., Eguchi Y., Shimizu S., Martinou J.C., and Tsujimoto Y. (1998) Death-signalling cascade in mouse cerebellar granule neurons. Eur. J. Neurosci. 10, 1403–1411.

    Article  PubMed  CAS  Google Scholar 

  232. Tanaka M., Sawada M., Yoshida S., Hanaoka F., and Marunouchi T. (1995) Insulin prevents apoptosis of external granular layer neurons in rat cerebellar slice cultures. Neurosci. Lett. 199, 37–40.

    Article  PubMed  CAS  Google Scholar 

  233. Tanaka M., Sawada M., Miura M., and Marunouchi T. (1998) Insulin-like growth factor-I analogue prevents apoptosis mediated through an interleukin-1 beta converting enzyme (caspase-1)-like protease of cerebellar external granular layer neurons: developmental stage-specific mechanisms of neuronal cell death. Neuroscience 84, 89–100.

    Article  PubMed  CAS  Google Scholar 

  234. Torres-Aleman I., Naftolin F., and Robbins R.J. (1990) Trophic effects of insulin-like growth factor-I on fetal rat hypothalamic cells in culture. Neuroscience 35, 601–608.

    Article  PubMed  CAS  Google Scholar 

  235. Torres-Aleman I., Villalba M., and Nieto-Bona M.P. (1998) Insulin-like growth factor-I modulation of cerebellar cell populations is developmentally stage-dependent and mediated by specific intracellular pathways. Neuroscience 83, 321–334.

    Article  PubMed  CAS  Google Scholar 

  236. Tranque P., Naftolin F., and Robbins R. (1994) Differential regulation of astrocyte plasminogen activators by insulin-like growth factor-I and epidermal growth factor. Endocrinology 134, 2606–2613.

    Article  PubMed  CAS  Google Scholar 

  237. Vergani L., Di Giulio A.M., Losa M., Rossoni G., Muller E.E., and Gorio A. (1998) Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation. J. Neurosci. Res. 54, 840–847.

    Article  PubMed  CAS  Google Scholar 

  238. Vergeli M., Mazzanti B., Ballerini C., Gran B., Amaducci L., and Massacesi L. (1995) Transforming growth factor-beta 1 inhibits the proliferation of rat astrocytes induced by serum and growth factors. J. Neurosci. Res. 40, 127–133.

    Article  PubMed  CAS  Google Scholar 

  239. Wan Q., Xiong Z.G., Man H.Y., Ackerley C.A., Braunton J., Lu W.Y., et al. (1997) Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin. Nature 388, 686–690.

    Article  PubMed  CAS  Google Scholar 

  240. Wang J.M., Hayashi T., Zhang W.R., Sakai K., Shiro Y., and Abe K. (2000) Reduction of ischemic brain injury by topical application of insulin-like growth factor-I after transient middle cerebral artery occlusion in rats. Brain Res. 859, 381–385.

    Article  PubMed  CAS  Google Scholar 

  241. Yamada M., Tanabe K., Wada K., Shimoke K., Ishikawa Y., Ikeuchi T., et al. (2001) Differences in survival-promoting effects and intracellular signaling properties of BDNF and IGF-1 in cultured cerebral cortical neurons. J. Neurochem. 78, 940–951.

    Article  PubMed  CAS  Google Scholar 

  242. Yamaguchi A., Tamatani M., Matsuzaki H., Namikawa K., Kiyama H., Vitek M.P., et al. (2001) Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53. J. Biol. Chem. 276, 5256–5264.

    Article  PubMed  CAS  Google Scholar 

  243. Yan H., Bunge M.B., Wood P.M., and Plant G.W. (2001) Mitogenic response of adult rat olfactory ensheathing glia to four growth factors. Glia 33, 334–342.

    Article  PubMed  CAS  Google Scholar 

  244. Yasuda T., Grinspan J., Stern J., Franceschini B., Bannerman P., and Pleasure D. (1995) Apoptosis occurs in the oligodendroglial lineage, and is prevented by basic fibroblast growth factor. J. Neurosci. Res. 40, 306–317.

    Article  PubMed  CAS  Google Scholar 

  245. Ye P., Li L., Richards R.G., DiAugustine R.P., and D’Ercole A.J. (2002) Myelination is altered in insulin-like growth factor-I null mutant mice. J. Neurosci. 22, 6041–6051.

    PubMed  CAS  Google Scholar 

  246. Ye P., Carson J., and D’Ercole A.J. (1995) Insulin-like growth factor-I influences the initiation of myelination: studies of the anterior commissure of transgenic mice. Neurosci. Lett. 201, 235–238.

    Article  PubMed  CAS  Google Scholar 

  247. Ye P., Carson J., and D’Ercole A.J. (1995) In vivo actions of insulin-like growth factor-I (IGF-I) on brain myelination: studies of IGF-I and IGF binding protein-I (IGFBP-I) transgenic mice. J. Neurosci. 15, 7344–7356.

    PubMed  CAS  Google Scholar 

  248. Ye P., Xing Y., Dai Z., and D’Ercole A.J. (1996) In vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development in transgenic mice: evidence that IGF-I increases proliferation of granule cell progenitors. Brain Res. Dev. Brain Res. 95, 44–54.

    Article  PubMed  CAS  Google Scholar 

  249. Ye P. and D’Ercole A.J. (1999) Insulin-like growth factor I protects oligodendrocytes from tumor necrosis factor-alpha-induced injury. Endocrinology 140, 3063–3072.

    Article  PubMed  CAS  Google Scholar 

  250. Zackenfels K., Oppenheim R.W., and Rohrer H. (1995) Evidence for an important role of IGF-I and IGF-II for the early development of chick sympathetic neurons. Neuron 14, 731–741.

    Article  PubMed  CAS  Google Scholar 

  251. Zawada W.M., Kirschman D.L., Cohen J.J., Heidenreich K.A., and Freed C.R. (1996) Growth factors rescue embryonic dopamine neurons from programmed cell death. Exp. Neurol. 140, 60–67.

    Article  PubMed  CAS  Google Scholar 

  252. Trejo J.L., Carro E., and Torres-Aleman I. (2001) Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J. Neurosci. 21, 1628–1634.

    PubMed  CAS  Google Scholar 

  253. Arsenijevic Y. and Weiss S. (1998) Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor. J. Neurosci. 18, 2118–2128.

    PubMed  CAS  Google Scholar 

  254. Gutierrez-Ospina G., Calikoglu A.S., Ye P., and D’Ercole A.J. (1996) In vivo effects of insulin-like growth factor-I on the development of sensory pathways: analysis of the primary somatic sensory cortex (S1) of transgenic mice. Endocrinology 137, 5484–5492.

    Article  PubMed  CAS  Google Scholar 

  255. Mason J.L., Ye P., Suzuki K., D’Ercole A.J., and Matsushima G.K. (2000) Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J. Neurosci. 20, 5703–5708.

    PubMed  CAS  Google Scholar 

  256. Ye P., Lee K.H., and D’Ercole A.J. (2000) Insulin-like growth factor-I (IGF-I) protects myelination from undernutritional insult: studies of transgenic mice overexpressing IGF-I in brain. J. Neurosci. Res. 62, 700–708.

    Article  PubMed  CAS  Google Scholar 

  257. Leon Y., Sanz C., Giraldez F., and Varela-Nieto I. (1998) Induction of cell growth by insulin and insulin-like growth factor-I is associated with Jun expression in the otic vesicle. J. Comp. Neurol. 398, 323–332.

    Article  PubMed  CAS  Google Scholar 

  258. Sonntag W.E., Lynch C., Thornton P., Khan A., Bennett S., and Ingram R. (2000) The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. J. Anat. 197, 575–585.

    Article  PubMed  CAS  Google Scholar 

  259. Anderson M.J., Rossetto D.L., and Lorenz L.A. (1994) Neuronal differentiation in vitro from precursor cells of regenerating spinal cord of the adult teleost Apteronotus albifrons. Cell Tissue Res. 278, 243–248.

    PubMed  CAS  Google Scholar 

  260. Woods K.A., Camacho-Hubner C., Savage A.O., and Clark A.J.L. (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N. Engl. J. Med. 335, 1363–1367.

    Article  PubMed  CAS  Google Scholar 

  261. Dore S., Kar S., and Quirion R. (1997) Rediscovering an old friend, IGF-I: potential use in the treatment of neurodegenerative diseases. Trends Neurosci. 20, 326–331.

    Article  PubMed  CAS  Google Scholar 

  262. Savage M.O., Camacho-Hubner C., Dunger D.B., Ranke M.B., Ross R.J., and Rosenfeld R.G. (2001) Is there a medical need to explore the clinical use of insulin-like growth factor I? Growth Horm. IGF Res. 11, S65-S69.

    Article  PubMed  Google Scholar 

  263. Liu J.L. and LeRoith D. (1999) Insulin-like growth factor I is essential for postnatal growth in response to growth hormone. Endocrinology 140, 5178–5184.

    Article  PubMed  CAS  Google Scholar 

  264. Bohni R., Riesgo-Escovar J., Oldham S., Brogiolo W., Stocker H., Andruss B.F., et al. (1999) Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97, 865–875.

    Article  PubMed  CAS  Google Scholar 

  265. Gee C.E. and Robertson R.M. (2001) Insulin-like peptides are not involved in maturation or functional recovery of neural circuits in the locust flight system. Can. J. Physiol. Pharmacol. 79, 362–366.

    Article  PubMed  CAS  Google Scholar 

  266. Carter C.S., Ramsey M.M., and Sonntag W.E. (2002) A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan. Trends Genet. 18, 295–301.

    Article  PubMed  CAS  Google Scholar 

  267. Cho Y., Gong T.W., Stover T., Lomax M.I., and Altschuler R.A. (2002) Gene expression profiles of the rat cochlea, cochlear nucleus, and inferior colliculus. J. Assoc. Res. Otolaryngol. 3, 54–67.

    Article  PubMed  Google Scholar 

  268. Hsieh C.C., DeFord J.H., Flurkey K., Harrison D.E., and Papaconstantinou J. (2002) Implications for the insulin signaling pathway in Snell dwarf mouse longevity: a similarity with the C. elegans longevity paradigm. Mech. Ageing Dev. 123, 1229–1244.

    PubMed  CAS  Google Scholar 

  269. Lawlor M.A., Mora A., Ashby P.R., Williams M.R., Murray-Tait V., Malone L., et al. (2002) Essential role of PDK1 in regulating cell size and development in mice. EMBO J. 21, 3728–3738.

    Article  PubMed  CAS  Google Scholar 

  270. Saucedo L. and Edgar B. (2002) Why size matters: altering cell size. Curr. Opin. Genet. Dev. 12, 565.

    Article  PubMed  CAS  Google Scholar 

  271. Holzenberger M., Dupont J., Ducos B., Leneuve P., Geloen A., Even P.C., et al. (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421, 182–187.

    Article  PubMed  CAS  Google Scholar 

  272. Mathonnet M., Comte I., Lalloue F., and Ayer-Le L.C. (2001) Insulin-like growth factor I induced survival of axotomized olfactory neurons in the chick. Neurosci. Lett. 308, 67–70.

    Article  PubMed  CAS  Google Scholar 

  273. Rajkumar K., Barron D., Lewitt M.S., and Murphy L.J. (1995) Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136, 4029–4034.

    Article  PubMed  CAS  Google Scholar 

  274. Burns J.L. and Hassan A.B. (2001) Cell survival and proliferation are modified by insulin-like growth factor 2 between days 9 and 10 of mouse gestation. Development 128, 3819–3830.

    PubMed  CAS  Google Scholar 

  275. Constancia M., Hemberger M., Hughes J., Dean W., Ferguson-Smith A., Fundele R., et al. (2002) Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 417, 945–948.

    Article  PubMed  CAS  Google Scholar 

  276. Konishi Y., Takahashi K., Chui D.H., Rosenfeld R.G., Himeno M., and Tabira T. (1994) Insulin-like growth factor II promotes in vitro cholinergic development of mouse septal neurons: comparison with the effects of insulin-like growth factor I. Brain Res. 649, 53–61.

    Article  PubMed  CAS  Google Scholar 

  277. Vicario-Abejon C., Yusta-Boyo M.J., Fernández-Moreno C., and de Pablo F. (2002) Locally-born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous IGF-I for differentiation into neurons and glia. J. Neurosci. 23, 895–906.

    Google Scholar 

  278. Pichel J.G., Fernandez-Moreno C., Vicario-Abejon C., Testillano P.S., Patterson P.H., and de Pablo F. (2002) Developmental cooperation of Leukemia Inhibitor Factor and Insulin-Like Growth Factor I in mice is tissue-specific and essential for lung maturation. Mech. Dev. 120, 349–361.

    Article  Google Scholar 

  279. Fischer A.J., McGuire C.R., Dierks B.D., and Reh T.A. (2002) Insulin and Fibroblast Growth Factor 2 activate a neurogenic program in Muller glia of the chicken retina. J. Neurosci. 22, 9387–9398.

    PubMed  CAS  Google Scholar 

  280. de Pablo F., Banner L.R., and Patterson P.H. (2000) IGF-1 expression is decreased in LIF-deficient mice after peripheral nerve injury. Neuroreport 11, 1365–1368.

    Article  PubMed  Google Scholar 

  281. Markowska A.L., Mooney M., and Sonntag W.E. (1998) Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience 87, 559–569.

    Article  PubMed  CAS  Google Scholar 

  282. Carro E., Nunez A., Busiguina S., and Torres-Aleman I. (2000) Circulating insulin-like growth factor I mediates effects of exercise on the brain. J. Neurosci. 20, 2926–2933.

    PubMed  CAS  Google Scholar 

  283. Lewis M.E., Neff N.T., Contreras P.C., Stong D.B., Oppenheim R.W., Grebow P.E., et al. (1993) Insulin-like growth factor-I: potential for treatment of motor neuronal disorders. Exp. Neurol. 124, 73–88.

    Article  PubMed  CAS  Google Scholar 

  284. Sanz C., Leon Y., Canon S., Alvarez L., Giraldez F., and Varela-Nieto I. (1999) Pattern of expression of the jun family of transcription factors during the early development of the inner ear: implications in apoptosis. J. Cell Sci. 112, 3967–3974.

    PubMed  CAS  Google Scholar 

  285. Sanz C., Leon Y., Troppmair J., Rapp U.R., and Varela-Nieto I. (1999) Strict regulation of c-Raf kinase levels is required for early organogenesis of the vertebrate inner ear. Oncogene 18, 429–437.

    Article  PubMed  CAS  Google Scholar 

  286. Frago L.M., Camerero G., Canon S., Paneda C., Sanz C., Leon Y., et al. (2000) Role of diffusible and transcription factors in inner ear development: implications in regeneration. Histol. Histopathol. 15, 657–666.

    PubMed  CAS  Google Scholar 

  287. Kopke R.D., Jackson R.L., Li G., Rasmussen M.D., Hoffer M.E., Frenz D.A., et al. (2001) Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function. Proc. Natl. Acad. Sci. USA 98, 5886–5891.

    Article  PubMed  CAS  Google Scholar 

  288. Oesterle E.C., Tsue T.T., and Rubel E.W. (1997) Induction of cell proliferation in avian inner ear sensory epithelia by insulin-like growth factor-I and insulin. J. Comp. Neurol. 380, 262–274.

    Article  PubMed  CAS  Google Scholar 

  289. Brunet A., Datta S.R., and Greenberg M.E. (2001) Transcription-dependent and — independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr. Opin. Neurobiol. 11, 297–305.

    Article  PubMed  CAS  Google Scholar 

  290. Cantrell D. (2002) Protein kinase B (Akt) regulation and function in T lymphocytes. Semin. Immunol. 14, 19–26.

    Article  PubMed  CAS  Google Scholar 

  291. Lawlor M.A. and Alessi D.R. (2001) PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J. Cell Sci. 114, 2903–2910.

    PubMed  CAS  Google Scholar 

  292. Strle K., Zhou J.H., Broussard S.R., Venters H.D., Johnson R.W., Freund G.G., et al. (2002) IL-10 promotes survival of microglia without activating Akt. J. Neuroimmunol. 122, 9–19.

    Article  PubMed  CAS  Google Scholar 

  293. Kaytor M.D. and Orr H.T. (2002) The GSK3 beta signaling cascade and neurodegenerative disease. Curr. Opin. Neurobiol. 12, 275–278.

    Article  PubMed  CAS  Google Scholar 

  294. Cheng C.M., Reinhardt R.R., Lee W.H., Joncas G., Patel S.C., and Bondy C.A. (2000) Insulinlike growth factor 1 regulates developing brain glucose metabolism. Proc. Natl. Acad. Sci. USA 97, 10,236–10,241.

    Article  CAS  Google Scholar 

  295. Moses A.C. (2002) Recombinant insulin-like growth factor-I as therapy in states of altered carbohydrate homeostasis. Curr. Opin. Endocrinol. Diabetes 4, 16–25.

    Google Scholar 

  296. Humbert S., Bryson E.A., Cordelieres F.P., Connors N.C., Datta S.R., Finkbeiner S., et al. (2002) The IGF-1/Akt pathway is neuroprotective in Huntington’s disease and involves Huntingtin phosphorylation by Akt. Dev. Cell 2, 831–837.

    Article  PubMed  CAS  Google Scholar 

  297. Clawson T.F., Vannucci S.J., Wang G.M., Seaman L.B., Yang X.L., and Lee W.H. (1999) Hypoxia-ischemia-induced apoptotic cell death correlates with IGF-I mRNA decrease in neonatal rat brain. Biol. Signals Recept. 8, 281–293.

    Article  PubMed  CAS  Google Scholar 

  298. Lackey B.R., Gray S.L., and Henricks D.M. (2000) Actions and interactions of the IGF system in Alzheimer’s disease: review and hypotheses. Growth Horm. IGF Res. 10, 1–13.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Arturo Duperier 4, E-28029, Madrid, Spain

    Isabel Varela-Nieto & Yolanda León

  2. Centro de Investigaciones Biológicas, CSIC, Velázquez 144, E-28006, Madrid, Spain

    Enrique J. de la Rosa & Ana I. Valenciano

Authors
  1. Isabel Varela-Nieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enrique J. de la Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana I. Valenciano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yolanda León
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabel Varela-Nieto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Varela-Nieto, I., de la Rosa, E.J., Valenciano, A.I. et al. Cell death in the nervous system. Mol Neurobiol 28, 23–49 (2003). https://doi.org/10.1385/MN:28:1:23

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:28:1:23

Index Entries

Search

Navigation