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Genetic Analysis of CNS Remyelination

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Advances in multiple Sclerosis and Experimental Demyelinating Diseases

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 318))

Myelin repair (remyelination) following the demyelination of central nervous system (CNS) axons in diseases such as multiple sclerosis plays a critical role in determining the level of accompanying neurologic disability. While remyelination can be quite robust, in multiple sclerosis it often fails. Understanding and stimulating the remyelination process are therefore important goals in MS research. Remyelination is a complex cellular process that involves an intimate interplay between the myelin-producing cells of the CNS (oligodendrocytes), the axons to be myelinated, as well as CNS-infiltrating immune cells. Genetic analysis can be a powerful tool for the functional analysis of complex cellular processes and has recently been applied to the problem of remyelination failure during disease. This chapter reviews the recent use of genetic approaches for the study of CNS remyelination in mouse models of demyelinating disease.

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References

  1. Allayee H, Andalibi A, Mehrabian M (2006) Using inbred mouse strains to identify genes for complex diseases. Front Biosci 11:1216-1226

    Article  CAS  PubMed  Google Scholar 

  2. Argaw AT, Zhang Y, Snyder BJ, Zhao ML, Kopp N, Lee SC, Raine CS, Brosnan CF, John GR (2006) IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J Immunol 177:5574-5584

    CAS  PubMed  Google Scholar 

  3. Armstrong RC, Le TQ, Flint NC, Vana AC, Zhou YX (2006) Endogenous cell repair of chronic demyelination. J Neuropathol Exp Neurol 65:245-256

    PubMed  Google Scholar 

  4. Armstrong RC, Le TQ, Frost EE, Borke RC, Vana AC (2002) Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. J Neurosci 22:8574-8585

    CAS  PubMed  Google Scholar 

  5. Baerwald KD, Popko B (1998) Developing and mature oligodendrocytes respond differently to the immune cytokine interferon-gamma. J Neurosci Res 52:230-239

    Article  CAS  PubMed  Google Scholar 

  6. Balabanov R, Strand K, Kemper A, Lee JY, Popko B (2006) Suppressor of cytokine signaling 1 expression protects oligodendrocytes from the deleterious effects of interferon-gamma. J Neurosci 26:5143-5152

    Article  CAS  PubMed  Google Scholar 

  7. Benninger Y, Colognato H, Thurnherr T, Franklin RJ, Leone DP, Atanasoski S, Nave KA, Ffrench-Constant C, Suter U, Relvas JB (2006) Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination. J Neurosci 26:7665-7673

    Article  CAS  PubMed  Google Scholar 

  8. Betz UA, Vosshenrich CA, Rajewsky K, Muller W (1996) Bypass of lethality with mosaic mice generated by cre-loxP-mediated recombination. Curr Biol 6:1307-1316

    Article  CAS  PubMed  Google Scholar 

  9. Bieber AJ, Kerr S, Rodriguez M (2003) Efficient central nervous system remyelination requires T cells. Ann Neurol 53:680-684

    Article  PubMed  Google Scholar 

  10. Bieber AJ, Rodriguez M (2003) Experimental models of virus-induced demyelination. In: Griffin J, Lassmann H, Nave K-A, Trapp B, Lazzarini R, Miller R (eds) Myelin and Its Diseases. Academic Press, New York, pp. 1073-1100.

    Google Scholar 

  11. Bieber AJ, Ure DR, Rodriguez M (2005) Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis. J Neuropathol Exp Neurol 64:46-57

    CAS  PubMed  Google Scholar 

  12. Bieber AJ, Warrington A, Asakura K, Ciric B, Kaveri SV, Pease LR, Rodriguez M (2002) Human antibodies accelerate the rate of remyelination following lysolecithin-induced demyelination in mice. Glia 37:241-249

    Article  PubMed  Google Scholar 

  13. Bjartmar C, Trapp BD (2001) Axonal and neuronal degeneration in multiple sclerosis: Mechanisms and functional consequences. Curr Opin Neurol 14:271-278

    Article  CAS  PubMed  Google Scholar 

  14. Bjartmar C, Trapp BD (2003) Axonal degeneration and progressive neurologic disability in multiple sclerosis. Neurotox Res 5:157-164

    Article  PubMed  Google Scholar 

  15. Brosnan CF, Cannella B, Battistini L, Raine CS (1995) Cytokine localization in multiple sclerosis lesions: Correlation with adhesion molecule expression and reactive nitrogen species. Neurology 45:S16-S21

    CAS  PubMed  Google Scholar 

  16. Colognato H, Baron W, Avellana-Adalid V, Relvas JB, Baron-Van Evercooren A, GeorgesLabouesse E, Ffrench-Constant C (2002) CNS integrins switch growth factor signalling to promote target-dependent survival. Nat Cell Biol 4:833-841

    Article  CAS  PubMed  Google Scholar 

  17. Corbin JG, Kelly D, Rath EM, Baerwald KD, Suzuki K,Popko B (1996) Targeted CNS expression of interferon-gamma in transgenic mice leads to hypomyelination, reactive gliosis, and abnormal cerebellar development. Mol Cell Neurosci 7:354-370

    Article  CAS  PubMed  Google Scholar 

  18. Crang AJ, Blakemore WF (1991) Remyelination of demyelinated rat axons by transplanted mouse oligodendrocytes. Glia 4:305-313

    Article  CAS  PubMed  Google Scholar 

  19. Franklin RJ (2002) Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 3:705-714

    Article  CAS  PubMed  Google Scholar 

  20. Frost EE, Buttery PC, Milner R, ffrench-Constant C (1999) Integrins mediate a neuronal survival signal for oligodendrocytes. Curr Biol 9:1251-1254

    Article  CAS  PubMed  Google Scholar 

  21. Gold R, Hartung HP, Toyka KV (2000) Animal models for autoimmune demyelinating disorders of the nervous system. Mol Med Today 6:88-91

    Article  CAS  PubMed  Google Scholar 

  22. Hall SM (1972) The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci 10:535-546

    CAS  PubMed  Google Scholar 

  23. Harding HP, Zeng H, Zhang Y, Jungries R, Chung P, Plesken H, Sabatini DD, Ron D (2001) Diabetes mellitus and exocrine pancreatic dysfunction in PERK-/- mice reveals a role for translational control in secretory cell survival. Mol Cell 7:1153-1163

    Article  CAS  PubMed  Google Scholar 

  24. Horwitz MS, Evans CF, McGavern DB, Rodriguez M, Oldstone MB (1997) Primary demyelination in transgenic mice expressing interferon-gamma. Nat Med 3:1037-1041

    Article  CAS  PubMed  Google Scholar 

  25. Jeffery ND, Blakemore WF (1995) Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin. J Neurocytol 24:775-781

    Article  CAS  PubMed  Google Scholar 

  26. Kile BT, Hilton DJ (2005) The art and design of genetic screens: Mouse. Nat Rev Genet 6:557-567

    Article  CAS  PubMed  Google Scholar 

  27. Levine JM, Reynolds R, Fawcett JW (2001) The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24:39-47

    Article  CAS  PubMed  Google Scholar 

  28. Lin W, Harding HP, Ron D, Popko B (2005) Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-gamma. J Cell Biol 169:603-612

    Article  CAS  PubMed  Google Scholar 

  29. Lin W, Kemper A, Dupree JL, Harding HP, Ron D, Popko B (2006) Interferon-gamma inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stress. Brain 129:1306-1318

    Article  PubMed  Google Scholar 

  30. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann Neurol 47:707-717

    Article  CAS  PubMed  Google Scholar 

  31. Mason JL, Suzuki K, Chaplin DD, Matsushima GK (2001) Interleukin-1beta promotes repair of the CNS. J Neurosci 21:7046-7052

    CAS  PubMed  Google Scholar 

  32. Mason JL, Ye P, Suzuki K, D’Ercole AJ, Matsushima GK (2000) Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J Neurosci 20:5703-5708

    CAS  PubMed  Google Scholar 

  33. Matsushima GK, Morell P (2001) The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol 11:107-116

    CAS  PubMed  Google Scholar 

  34. Matthews AE, Weiss SR, Paterson Y (2002) Murine hepatitis virus - A model for virusinduced CNS demyelination. J Neurovirol 8:76-85

    Article  CAS  PubMed  Google Scholar 

  35. Merrill JE (1991) Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. Dev Neurosci 13:130-137

    Article  CAS  PubMed  Google Scholar 

  36. Murtie JC, Zhou YX, Le TQ, Vana AC, Armstrong RC (2005) PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination. Neurobiol Dis 19:171-182

    Article  CAS  PubMed  Google Scholar 

  37. Panitch HS (1992) Interferons in multiple sclerosis. A review of the evidence. Drugs 44:946-962

    Article  CAS  PubMed  Google Scholar 

  38. Panitch HS, Hirsch RL, Schindler J, Johnson KP (1987) Treatment of multiple sclerosis with gamma interferon: Exacerbations associated with activation of the immune system. Neurology 37:1097-1102

    CAS  PubMed  Google Scholar 

  39. Potocnik AJ, Brakebusch C, Fassler R (2000) Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow. Immunity 12:653-663

    Article  CAS  PubMed  Google Scholar 

  40. Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES (1993) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137-151

    Article  CAS  PubMed  Google Scholar 

  41. Prineas JW, Connell F (1979) Remyelination in multiple sclerosis. Ann Neurol 5:22-31

    Article  CAS  PubMed  Google Scholar 

  42. Rajewsky K, Gu H, Kuhn R, Betz UA, Muller W, Roes J, Schwenk F (1996) Conditional gene targeting. J Clin Invest 98:600-603

    Article  CAS  PubMed  Google Scholar 

  43. Relvas JB, Setzu A, Baron W, Buttery PC, LaFlamme SE, Franklin RJ, Ffrench-Constant C (2001) Expression of dominant-negative and chimeric subunits reveals an essential role for beta1 integrin during myelination. Curr Biol 11:1039-1043

    Article  CAS  PubMed  Google Scholar 

  44. Ristevski S (2005) Making better transgenic models: Conditional, temporal, and spatial approaches. Mol Biotechnol 29:153-163

    Article  CAS  PubMed  Google Scholar 

  45. Schwartz M (2000) Beneficial autoimmune T cells and posttraumatic neuroprotection. Ann N Y Acad Sci 917:341-347

    CAS  PubMed  Google Scholar 

  46. Schwartz M, Moalem G, Leibowitz-Amit R, Cohen IR (1999) Innate and adaptive immune responses can be beneficial for CNS repair. Trends Neurosci 22:295-299

    Article  CAS  PubMed  Google Scholar 

  47. Stohlman SA, Hinton DR (2001) Viral induced demyelination. Brain Pathol 11:92-106

    Article  CAS  PubMed  Google Scholar 

  48. Van der Neut R (1997) Targeted gene disruption: Applications in neurobiology. J Neurosci Methods 71:19-27

    Article  CAS  PubMed  Google Scholar 

  49. Woodruff RH, Fruttiger M, Richardson WD, Franklin RJ (2004) Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult CNS and their response following CNS demyelination. Mol Cell Neurosci 25:252-262

    Article  CAS  PubMed  Google Scholar 

  50. Ye P, Carson J, D’Ercole AJ (1995) In vivo actions of insulin-like growth factor-1 (IGF-1) on brain myelination: Studies of IGF-1 and IGF binding protein-1 (IGFBP-1) transgenic mice. J Neurosci 15:7344-7356

    CAS  PubMed  Google Scholar 

  51. Yoshida H (2007) ER stress and diseases. FEBS J 274:630-658

    Article  CAS  PubMed  Google Scholar 

  52. Zhang P, McGrath B, Li S, Frank A, Zambito F, Reinert J, Gannon M, Ma K, McNaughton K, Cavener DR (2002) The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol Cell Biol 22:3864-3874

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA

    A. J. Bieber

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  1. A. J. Bieber
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Editors and Affiliations

  1. Department of Neurology and Immunology, Mayo Clinic, College of Medicine, 200 First Street SW, Rochester, MN 55905, USA

    Moses Rodriguez

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© 2008 Springer-Verlag Berlin Heidelberg

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Bieber, A.J. (2008). Genetic Analysis of CNS Remyelination. In: Rodriguez, M. (eds) Advances in multiple Sclerosis and Experimental Demyelinating Diseases. Current Topics in Microbiology and Immunology, vol 318. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73677-6_7

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