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Regulation of Oligodendrocyte Development and CNS Myelination by IGF-I: Prospects for Disease Therapy

  • F. A. Mcmorris
  • G. S. Vemuri
  • É. Boyle-Walsh
  • R. Mewar
  • M. J. Engleka
  • G. Lesh

Abstract

Myelin is an innovation that arose relatively recently during evolution, being found only in vertebrates and not in lower taxa. In axons ensheathed by myelin, which forms a series of insulating segments or “internodes” separated by uninsulated nodes of Ranvier, action potentials are conducted in saltatory fashion, jumping from one node of Ranvier to the next without depolarizing the axonal membrane covered by the intervening myelin. As a result, thin myelinated axons can conduct action potentials at the same velocity as much thicker unmyelinated axons, allowing considerable savings in space without sacrificing performance. Moreover, because membrane depolarization and ion flux occur only at the nodes of Ranvier, myelin reduces the energy cost of conduction by a factor of 100 or more. Without the miniaturization and energy efficiency enabled by myelination, the highly complex nervous systems of vertebrates would not be possible. The importance of myelin to neural function is strikingly illustrated by the devastating consequences of demyelination in multiple sclerosis (MS). However, in spite of myelin’s fundamental role in nervous system function and its involvement in MS and other human diseases, relatively little is known about the regulation of myelin production by the myelin-forming cells of the central and peripheral nervous systems (CNS and PNS), oligodendrocytes and Schwann cells, respectively. Clarification of these processes would give us a better fundamental understanding of nervous system development and function, and would likely yield information useful in designing therapies to promote remyelination in MS and other myelin diseases.

Keywords

Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Docking Protein Oligodendroglial Cell Oligodendrocyte Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    McMorris FA, Smith TM, DeSalvo S, Furlanetto RW (1986) Insulin-like growth factor I/somatomedin C: A potent inducer of oligodendrocyte development. Proc Natl Acad Sci USA 83: 822–826Google Scholar
  2. 2.
    McMorris FA, Furlanetto RW (1989) Insulin-like growth factor II induces development of oligodendrocytes from rat brain. The Endocrine Society, 71st Annual Meeting, A603Google Scholar
  3. 3.
    McMorris FA, Furlanetto RW, Mozell RL, Carson MJ, Raible DW (1990) Regulation of oligodendrocyte development by insulin-like growth factors and cyclic nucleotides. Ann N Y Acad Sci 605: 101–109PubMedCrossRefGoogle Scholar
  4. 4.
    McMorris FA, Dubois-Dalcq M (1988) Insulin-like growth factor I promotes cell proliferation and oligodendroglial commitment in rat glial progenitor cells developing in vitro. J Neurosci Res 21: 199–209PubMedCrossRefGoogle Scholar
  5. 5.
    McMorris FA, Mozell RL, Carson MJ, Shinar Y, Meyer RD, Marchetti N (1993) Regulation of oligodendrocyte development and central nervous system myelination by insulin-like growth factors. Ann N Y Acad Sci 692: 321–334PubMedCrossRefGoogle Scholar
  6. 6.
    Barres BA, Hart IK, Coles HSR, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992) Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70: 31–46PubMedCrossRefGoogle Scholar
  7. 7.
    Mozell RL, McMorris FA (1991) Insulin-like growth factor I stimulates oligodendrocyte development and myelination in rat brain aggregate cultures. J. Neurosci Res 30: 382–390PubMedCrossRefGoogle Scholar
  8. 8.
    Carson MJ, Behringer RR, Brinster RL, McMorris FA (1993) Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron 10: 729–740PubMedCrossRefGoogle Scholar
  9. 9.
    Meyer RD, Marchetti N, McMorris FA (1993) IGF-I increases CNP activity and mRNA per oligodendrocyte. Trans Am Soc Neurochem 24: 261Google Scholar
  10. 10.
    Carson M, Behringer RR, Mathews LS, Palmiter RD, Brinster RL, McMorris FA (1989) Hypomyelination caused by growth hormone deficiency is reversed by insulin-like growth factor I in transgenic mice. Trans Am Soc Neurochem 20: 286Google Scholar
  11. 11.
    Bartlett WP, Li XS, Williams M, Benkovic S (1991) Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development. Dev Biol 147: 239–250PubMedCrossRefGoogle Scholar
  12. 12.
    Bondy CA (1991) Transient IGF-I gene expression during the maturation of functionally related central projection neurons. J Neurosci 11: 3442–3455PubMedGoogle Scholar
  13. 13.
    Ballotti R, Nielsen FC, Pringle N, Kowalski A, Richardson WD, Van Obberghen E, Gammeltoft S (1987) Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase. EMBO J 6: 3633–3639PubMedGoogle Scholar
  14. 14.
    Rotwein P, Burgess SK, Milbrandt JD, Krause JE (1988) Differential expression of insulin-like growth factor genes in rat central nervous system. Proc Natl Acad Sci USA 85: 265–269PubMedCrossRefGoogle Scholar
  15. 15.
    Shinar Y, McMorris FA (1995) Developing oligodendroglia express mRNA for insulinlike growth factor I, a regulator of oligodendrocyte development. J Neurosci Res 42: 516–527PubMedCrossRefGoogle Scholar
  16. 16.
    Kelley KM, Oh Y, Gargosky SE, Gucev Z, Matsumoto T, Hwa V, Ng L, Simpson DM, Rosenfeld RG (1996) Insulin-like growth factor-binding proteins ( IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 28: 619–637Google Scholar
  17. 17.
    LeRoith D (1996) Insulin-like growth factor receptors and binding proteins. Baillieres Clin Endocrinol Metab 10: 49–73PubMedCrossRefGoogle Scholar
  18. 18.
    Mewar R, McMorris FA (1997) Expression of insulin-like growth factor binding protein messenger RNAs in developing rat oligodendrocytes and astrocytes. J Neurosci Res (in press)Google Scholar
  19. 19.
    Liu X, Yao DL, Bondy CA, Brenner M, Hudson LD, Zhou J, Webster HD (1994) Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. Mol Cell Neurosci 5: 418–430PubMedCrossRefGoogle Scholar
  20. 20.
    McFarlin DE, McFarland HF (1982) Multiple sclerosis (first of two parts). N Engl J Med 307: 1183–1188PubMedCrossRefGoogle Scholar
  21. 21.
    McFarlin DE, McFarland HF (1982) Multiple sclerosis (second of two parts). N Engl J Med 307: 1246–1251PubMedCrossRefGoogle Scholar
  22. 22.
    McKhann GM (1982) Multiple sclerosis. Annu Rev Neurosci 5: 219–239PubMedCrossRefGoogle Scholar
  23. 23.
    Raine CS (1990) Multiple sclerosis: immunopathologic mechanisms in the progression and resolution of inflammatory demyelination. Res Publ Assoc Res Nerv Ment Dis 68: 37–54PubMedGoogle Scholar
  24. 24.
    Waksman BH (1989) Multiple sclerosis. Curr Opin Immunol 1: 733–739PubMedCrossRefGoogle Scholar
  25. 25.
    Prineas JW, Connell F (1979) Remyelination in multiple sclerosis. Ann Neurol 5: 22–31PubMedCrossRefGoogle Scholar
  26. 26.
    Prineas JW, Kwon EE, Goldenberg PZ, Ilyas AA, Quarles RH, Benjamins JA, Sprinkle TJ (1989) Multiple sclerosis. Oligodendrocyte proliferation and differentiation in fresh lesions. Lab Invest 61: 489–503Google Scholar
  27. 27.
    Prineas JW, Kwon EE, Goldenberg PZ, Cho ES, Sharer LR (1990) Interaction of astrocytes and newly formed oligodendrocytes in resolving multiple sclerosis lesions. Lab Invest 63: 624–636PubMedGoogle Scholar
  28. 28.
    Ludwin SK (1980) Chronic demyelination inhibits remyelination in the central nervous system. An analysis of contributing factors. Lab Invest 43: 382–387PubMedGoogle Scholar
  29. 29.
    Raine CS, Scheinberg LC (1988) On the immunopathology of plaque development and repair in multiple sclerosis. J Neuroimmunol 20: 189–201PubMedCrossRefGoogle Scholar
  30. 30.
    Raine CS, Moore GR, Hintzen R, Traugott U (1988) Induction of oligodendrocyte proliferation and remyelination after chronic demyelination. Relevance to multiple sclerosis. Lab Invest 59: 467–476Google Scholar
  31. 31.
    McMorris FA, McKinnon RD (1996) Regulation of oligodendrocyte development and CNS myelination by growth factors: prospects for therapy of demyelinating disease. Brain Pathol 6: 313–329PubMedCrossRefGoogle Scholar
  32. 32.
    Yao DL, Liu X, Hudson LD, Webster HD (1995) Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 92: 6190–6194PubMedCrossRefGoogle Scholar
  33. 33.
    Liu X, Yao DL, Webster HD (1995) Insulin-like growth factor I treatment reduces clinical deficits and lesion severity in acute demyelinating experimental autoimmune encephalomyelitis. Mult Scler 1: 2–9PubMedGoogle Scholar
  34. 34.
    Yao DL, West NR, Bondy CA, Brenner M, Hudson LD, Zhou J, Collins GH, Webster HD (1995) Cryogenic spinal cord injury induces astrocytic gene expression of insulinlike growth factor I and insulin-like growth factor binding protein 2 during myelin regeneration. J Neurosci Res 40: 647–659PubMedCrossRefGoogle Scholar
  35. 35.
    Yao DL, Liu X, Hudson LD, Webster HD (1996) Insulin-like growth factor-I given sub- cutaneously reduces clinical deficits, decreases lesion severity and upregulates synthesis of myelin proteins in experimental autoimmune encephalomyelitis. Life Sci 58: 1301–1306PubMedCrossRefGoogle Scholar
  36. 36.
    Bondy CA, Underwood LE, Clemmons DR, Guler HP, Bach MA, Skarulis M (1994) Clinical uses of insulin-like growth factor I. Ann Intern Med 120: 593–601PubMedGoogle Scholar
  37. 37.
    Vaught JL, Contreras PC, Miller M, Neff N (1998) Neurobiology of rhIGF-I: rationale for use in motor neuron disease. In: Muller EE (ed) IGFs in the Neurons System. Springer-Verlag, Berlin Heidelberg New York, pp 105–114Google Scholar
  38. 38.
    Silani V, Brioschi A, Sampietro A, Ciammola A, Pizzuti A, Scarlato G (1998) rhIGF-I for the treatment of neuromuscular disorders. In: Muller EE (ed) IGFs in the Neurons System. Springer-Verlag, Berlin Heidelberg New York, pp 115–126Google Scholar
  39. 39.
    White MF, Kahn CR (1994) The insulin signaling system. J Biol Chem 269: 1–4PubMedGoogle Scholar
  40. 40.
    Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (1996) A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature 379: 560–564PubMedCrossRefGoogle Scholar
  41. 41.
    Sun XJ, Wang LM, Zhang Y, Yenush L, Myers MG Jr, Glasheen E, Lane WS, Pierce JH, White MF (1995) Role of IRS-2 in insulin and cytokine signalling. Nature 377: 173–177PubMedCrossRefGoogle Scholar
  42. 42.
    Sun XJ, Pons S, Wang LM, Zhang Y, Yenush L, Burks D, Myers MG Jr, Glasheen E, Copeland NG, Jenkins NA, Pierce JH, White MF (1997) The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action. Mol Endocrinol 11: 251–262PubMedCrossRefGoogle Scholar
  43. 43.
    Lavan BE, Lane WS, Lienhard GE (1997) The 60-kDa phosphotyrosine protein in insulin-treated adipocytes is a new member of the insulin receptor substrate family. J Biol Chem 272: 11439–11443PubMedCrossRefGoogle Scholar
  44. 44.
    Waters SB, Pessin JE (1996) Insulin receptor substrate 1 and 2 (IRS1 and IRS2): what a tangled web we weave. Trends Cell Biol 6: 1–3PubMedCrossRefGoogle Scholar
  45. 45.
    Sun XJ, Pons S, Asano T, Myers MG Jr, Glasheen E, White MF (1996) The Fyn tyrosine kinase binds IRS-1 and forms a distinct signaling complex during insulin action. J Biol Chem 271: 10583–10587PubMedCrossRefGoogle Scholar
  46. 46.
    Vemuri GS, McMorris FA (1996) Oligodendrocytes and their precursors require phos- phatidylinositol 3-kinase signaling for survival. Development 122: 2529–2537PubMedGoogle Scholar
  47. 47.
    Boyle-Walsh E, Vemuri GS, Holgado-Madruga M, Wong AJ, McMorris FA (1997) Expression of IGF-I signalling molecules in developing rat oligodendrocytes. J Neurochem 69:S9AGoogle Scholar
  48. 48.
    Vemuri GS, Boyle-Walsh E, Holgado-Madruga M, Engleka MJ, Wong AJ, McMorris FA (1997) Insulin-like growth factor I signals to phosphatidylinositol 3-kinase through the receptor docking proteins IRS-1, IRS-2 and Gabl in developing oligodendroglial cells. (Manuscript in preparation)Google Scholar
  49. 49.
    Vemuri GS, Boyle-Walsh E, Holgado-Madruga M, Engleka MJ, Wong AJ, McMorris FA (1997) Association of phosphatidylinositol 3-kinase with insulin-like growth factor receptor docking proteins in oligodendroglial cells. J Neurochem 69:S9BGoogle Scholar
  50. 50.
    Araki E, Lipes MA, Patti ME, Bruning JC, Haag B, Johnson RS, Kahn CR (1994) Alternative pathway of insulin signalling in mice with targeted disruption of the IRS- 1 gene. Nature 372: 186–190PubMedCrossRefGoogle Scholar
  51. 51.
    Engleka M, Folli F, Winnay J, Kahn CR, McMorris FA (1996) Insulin-receptor sub-strate-1 is required for normal myelination. J Neurochem 66:S20AGoogle Scholar
  52. 52.
    Boyle-Walsh E, Engleka M, Vemuri GS, Holgado-Madruga M, Wiemelt AP, Folli F, Winnay J, Kahn CR, Wong AJ, McMorris FA (1997) Expression of IGF-I signalling molecules in developing rat oligodendrocytes. ( Manuscript in preparation)Google Scholar
  53. 53.
    Umemori H, Sato S, Yagi T, Aizawa S, Yamamoto T (1994) Initial events of myelination involve Fyn tyrosine kinase signalling. Nature 367: 572–576PubMedCrossRefGoogle Scholar
  54. 54.
    Maness PF (1992) Nonreceptor protein tyrosine kinases associated with neuronal development. Dev Neurosci 14: 257–270PubMedCrossRefGoogle Scholar
  55. 55.
    Kypta RM, Goldberg Y, Ulug ET, Courtneidge SA (1990) Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell 62: 481–492PubMedCrossRefGoogle Scholar
  56. 56.
    Boyle-Walsh E, Engleka M, Mewar R, Chen J, Stein P, McMorris FA (1996) Detection and cloning of proteins in developing brain that interact with Fyn tyrosine kinase. J Neurochem 66:S87DGoogle Scholar
  57. 57.
    Boyle-Walsh E, Engleka M, Lesh G, Stein P, McMorris FA (1997) Role of the Src-family protein tyrosine kinases Fyn, Src and Yes in oligodendrocyte development and myelination in vitro and in vivo (in preparation)Google Scholar

Copyright information

© Springer-Verlag Italia, Milano 1998

Authors and Affiliations

  • F. A. Mcmorris
    • 1
  • G. S. Vemuri
    • 1
  • É. Boyle-Walsh
    • 1
  • R. Mewar
    • 1
  • M. J. Engleka
    • 1
  • G. Lesh
    • 1
  1. 1.The Wistar InstitutePhiladelphiaUSA

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