Neuroscience Bulletin

, Volume 29, Issue 2, pp 216–228 | Cite as

Oligodendroglia and neurotrophic factors in neurodegeneration

  • Andrew N. Bankston
  • Mariana D. Mandler
  • Yue Feng


Myelination by oligodendroglial cells (OLs) enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders. However, accumulating evidence indicates that OLs also provide support to neurons via mechanisms beyond the insulating function of myelin. More importantly, an increasing volume of reports indicates defects of OLs in numerous neurodegenerative diseases, sometimes even preceding neuronal loss in pre-symptomatic episodes, suggesting that OL pathology may be an important mechanism contributing to the initiation and/or progression of neurodegeneration. This review focuses on the emerging picture of neuronal support by OLs in the pathogenesis of neurodegenerative disorders through diverse molecular and cellular mechanisms, including direct neuron-myelin interaction, metabolic support by OLs, and neurotrophic factors produced by and/or acting on OLs.


oligodendroglia neurodegenerative diseases neuron-glial communication neurotrophic factors myelination 


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  1. [1]
    Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol 2012, 8: 647–656.PubMedCrossRefGoogle Scholar
  2. [2]
    Matute C, Alberdi E, Ibarretxe G, Sánchez-Gómez MaV. Excitotoxicity in glial cells. Eur J Pharmacol 2002, 447: 239–246.PubMedCrossRefGoogle Scholar
  3. [3]
    You Y, Bai H, Wang C, Chen LW, Liu B, Zhang H, et al. Myelin damage of hippocampus and cerebral cortex in rat pentylenetetrazol model. Brain Res 2011, 1381: 208–216.PubMedCrossRefGoogle Scholar
  4. [4]
    Hobson GM, Garbern JY. Pelizaeus-Merzbacher disease, Pelizaeus-Merzbacher-like disease 1, and related hypomyelinating disorders. Semin Neurol 2012, 32: 62–67.PubMedCrossRefGoogle Scholar
  5. [5]
    Martins-de-Souza D. Proteome and transcriptome analysis suggests oligodendrocyte dysfunction in schizophrenia. J Psychiatr Res 2010, 44: 149–156.PubMedCrossRefGoogle Scholar
  6. [6]
    Schmitt A, Hasan A, Gruber O, Falkai P. Schizophrenia as a disorder of disconnectivity. Eur Arch Psychiatry Clin Neurosci 2011, 261: 150–154.CrossRefGoogle Scholar
  7. [7]
    Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci 2008, 31: 535–561.PubMedCrossRefGoogle Scholar
  8. [8]
    Byravan S, Foster LM, Phan T, Verity AN, Campagnoni AT. Murine oligodendroglial cells express nerve growth factor. Proc Natl Acad Sci U S A 1994, 91: 8812–8816.PubMedCrossRefGoogle Scholar
  9. [9]
    Dai X, Lercher LD, Clinton PM, Du Y, Livingston DL, Vieira C, et al. The trophic role of oligodendrocytes in the basal forebrain. J Neurosci 2003, 23: 5846–5853.PubMedGoogle Scholar
  10. [10]
    Dai X, Qu P, Dreyfus CF. Neuronal signals regulate neurotrophin expression in oligodendrocytes of the basal forebrain. Glia 2001, 34: 234–239.PubMedCrossRefGoogle Scholar
  11. [11]
    Du Y, Dreyfus CF. Oligodendrocytes as providers of growth factors. J Neurosci Res 2002, 68: 647–654.PubMedCrossRefGoogle Scholar
  12. [12]
    Linker R, Gold R, Luhder F. Function of neurotrophic factors beyond the nervous system: inflammation and autoimmune demyelination. Crit Rev Immunol 2009, 29: 43–68.PubMedCrossRefGoogle Scholar
  13. [13]
    Wilkins A, Majed H, Layfield R, Compston A, Chandran S. Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte-derived glial cell line-derived neurotrophic factor. J Neurosci 2003, 23: 4967–4974.PubMedGoogle Scholar
  14. [14]
    Wilkins A, Chandran S, Compston A. A role for oligodendrocyte-derived IGF-1 in trophic support of cortical neurons. Glia 2001, 36: 48–57.PubMedCrossRefGoogle Scholar
  15. [15]
    Linker RA, Maurer M, Gaupp S, Martini R, Holtmann B, Giess R, et al. CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nat Med 2002, 8: 620–624.PubMedCrossRefGoogle Scholar
  16. [16]
    Villoslada P, Genain CP. Role of nerve growth factor and other trophic factors in brain inflammation. Prog Brain Res 2004, 146: 403–414.PubMedCrossRefGoogle Scholar
  17. [17]
    VonDran MW, Singh H, Honeywell JZ, Dreyfus CF. Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion. J Neurosci 2011, 31: 14182–14190.PubMedCrossRefGoogle Scholar
  18. [18]
    Ishibashi T, Lee PR, Baba H, Fields RD. Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve. J Neurosci Res 2009, 87: 3343–3355.PubMedCrossRefGoogle Scholar
  19. [19]
    Spiegel I, Peles E. A new player in CNS myelination. Neuron 2006, 49: 777–778.PubMedCrossRefGoogle Scholar
  20. [20]
    Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 2012, 487: 443–448.PubMedCrossRefGoogle Scholar
  21. [21]
    Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998, 338: 278–285.PubMedCrossRefGoogle Scholar
  22. [22]
    De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, et al. Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 1998, 121: 1469–1477.PubMedCrossRefGoogle Scholar
  23. [23]
    Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 1999, 46: 296–304.PubMedCrossRefGoogle Scholar
  24. [24]
    Nave KA. Myelination and support of axonal integrity by glia. Nature 2010, 468: 244–252.PubMedCrossRefGoogle Scholar
  25. [25]
    Wilkins A, Kondo Y, Song J, Liu S, Compston A, Black JA, et al. Slowly progressive axonal degeneration in a rat model of chronic, nonimmune-mediated demyelination. J Neuropathol Exp Neurol 2010, 69: 1256–1269.PubMedCrossRefGoogle Scholar
  26. [26]
    Haider L, Fischer MT, Frischer JM, Bauer J, Höftberger R, Botond G, et al. Oxidative damage in multiple sclerosis lesions. Brain 2011, 134: 1914–1924.PubMedCrossRefGoogle Scholar
  27. [27]
    Mahad DJ, Ziabreva I, Campbell G, Lax N, White K, Hanson PS, et al. Mitochondrial changes within axons in multiple sclerosis. Brain 2009, 132: 1161–1174.PubMedCrossRefGoogle Scholar
  28. [28]
    Mahad D, Ziabreva I, Lassmann H, Turnbull D. Mitochondrial defects in acute multiple sclerosis lesions. Brain 2008, 131: 1722–1735.PubMedCrossRefGoogle Scholar
  29. [29]
    Campbell GR, Ohno N, Turnbull DM, Mahad DJ. Mitochondrial changes within axons in multiple sclerosis: an update. Curr Opin Neurol 2012, 25: 221–230.PubMedCrossRefGoogle Scholar
  30. [30]
    Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009, 132: 1175–1189.PubMedCrossRefGoogle Scholar
  31. [31]
    Stys PK, Waxman SG, Ransom BR. Na+-Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter. Ann Neurol 1991, 30: 375–380.PubMedCrossRefGoogle Scholar
  32. [32]
    Trapp BD, Stys PK. Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol 2009, 8: 280–291.PubMedCrossRefGoogle Scholar
  33. [33]
    Worku Hassen G, Feliberti J, Kesner L, Stracher A, Mokhtarian F. Prevention of axonal injury using calpain inhibitor in chronic progressive experimental autoimmune encephalomyelitis. Brain Res 2008, 1236: 206–215.CrossRefGoogle Scholar
  34. [34]
    Sathornsumetee S, McGavern DB, Ure DR, Rodriguez M. Quantitative ultrastructural analysis of a single spinal cord demyelinated lesion predicts total lesion load, axonal loss, and neurological dysfunction in a murine model of multiple sclerosis. Am J Pathol 2000, 157: 1365–1376.PubMedCrossRefGoogle Scholar
  35. [35]
    Franklin RJM, Ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 2008, 9: 839–855.PubMedCrossRefGoogle Scholar
  36. [36]
    Crawford DK, Mangiardi M, Xia X, Lopez-Valdes HE, Tiwari-Woodruff SK. Functional recovery of callosal axons following demyelination: a critical window. Neuroscience 2009, 164: 1407–1421.PubMedCrossRefGoogle Scholar
  37. [37]
    Matsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol 2001, 11: 107–116.PubMedCrossRefGoogle Scholar
  38. [38]
    Griffiths I, Klugmann M, Anderson T, Yool D, Thomson C, Schwab MH, et al. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 1998, 280: 1610–1613.PubMedCrossRefGoogle Scholar
  39. [39]
    Yin X, Crawford TO, Griffin JW, Tu Ph, Lee VM, Li C, et al. Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons. J Neurosci 1998, 18: 1953–1962.PubMedGoogle Scholar
  40. [40]
    Yang LJ, Zeller CB, Shaper NL, Kiso M, Hasegawa A, Shapiro RE, et al. Gangliosides are neuronal ligands for myelin-associated glycoprotein. Proc Natl Acad Sci U S A 1996, 93: 814–818.PubMedCrossRefGoogle Scholar
  41. [41]
    Pan B, Fromholt SE, Hess EJ, Crawford TO, Griffin JW, Sheikh KA, et al. Myelin-associated glycoprotein and complementary axonal ligands, gangliosides, mediate axon stability in the CNS and PNS: Neuropathology and behavioral deficits in single- and double-null mice. Exp Neurol 2005, 195: 208–217.PubMedCrossRefGoogle Scholar
  42. [42]
    Poliak S, Peles E. The local differentiation of myelinated axons at nodes of Ranvier. Nat Rev Neurosci 2003, 4: 968–980.PubMedCrossRefGoogle Scholar
  43. [43]
    Zhu H, Zhao L, Wang E, Dimova N, Liu G, Feng Y, et al. The QKI-PLP pathway controls SIRT2 abundance in CNS myelin. Glia 2012, 60: 69–82.PubMedCrossRefGoogle Scholar
  44. [44]
    Werner HB, Kuhlmann K, Shen S, Uecker M, Schardt A, Dimova K, et al. Proteolipid protein is required for transport of Sirtuin 2 into CNS myelin. J Neurosci 2007, 27: 7717–7730.PubMedCrossRefGoogle Scholar
  45. [45]
    Li W, Zhang B, Tang J, Cao Q, Wu Y, Wu C, et al. Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through Deacetylating α-tubulin. J Neurosci 2007, 27: 2606–2616.PubMedCrossRefGoogle Scholar
  46. [46]
    Oluich LJ, Stratton JA, Xing YL, Ng SW, Cate HS, Sah P, et al. Targeted ablation of oligodendrocytes induces axonal pathology independent of overt demyelination. J Neurosci 2012, 32: 8317–8330.PubMedCrossRefGoogle Scholar
  47. [47]
    Gelfo F, Tirassa P, De Bartolo P, Caltagirone C, Petrosini L, Angelucci F. Brain and serum levels of nerve growth factor in a rat model of Alzheimer’s disease. J Alzheimer’s Dis 2011, 25: 213–217.Google Scholar
  48. [48]
    Lorigados Pedre L, Pavon Fuentes N, Alvarez Gonzalez L, McRae A, Serrano Sanchez T, Blanco Lescano L, et al. Nerve growth factor levels in Parkinson disease and experimental parkinsonian rats. Brain Res 2002, 952: 122–127.PubMedCrossRefGoogle Scholar
  49. [49]
    Peng S, Wuu J, Mufson EJ, Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem 2005, 93: 1412–1421.PubMedCrossRefGoogle Scholar
  50. [50]
    Tasset I, Sanchez-Lopez F, Aguera E, Fernandez-Bolanos R, Sanchez FM, Cruz-Guerrero A, et al. NGF and nitrosative stress in patients with Huntington’s disease. J Neurol Sci 2012, 315: 133–136.PubMedCrossRefGoogle Scholar
  51. [51]
    Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev. Neurol 2009, 5: 311–322.PubMedCrossRefGoogle Scholar
  52. [52]
    Sarchielli P, Greco L, Stipa A, Floridi A, Gallai V. Brainderived neurotrophic factor in patients with multiple sclerosis. J Neuroimmunol 2002, 132: 180–188.PubMedCrossRefGoogle Scholar
  53. [53]
    Scalabrino G, Galimberti D, Mutti E, Scalabrini D, Veber D, De Riz M, et al. Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis. Brain Res 2010, 1333: 64–71.PubMedCrossRefGoogle Scholar
  54. [54]
    Matrone C, Ciotti MT, Mercanti D, Marolda R, Calissano P. NGF and BDNF signaling control amyloidogenic route and Abeta production in hippocampal neurons. Proc Natl Acad Sci U S A 2008, 105: 13139–13144.PubMedCrossRefGoogle Scholar
  55. [55]
    Capsoni S, Marinelli S, Ceci M, Vignone D, Amato G, Malerba F, et al. Intranasal “painless” human Nerve Growth Factors slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice. PLoS One 2012, 7: e37555.PubMedCrossRefGoogle Scholar
  56. [56]
    Ebert AD, Beres AJ, Barber AE, Svendsen CN. Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson’s disease. Exp Neurol 2008, 209: 213–223.PubMedCrossRefGoogle Scholar
  57. [57]
    Ebert AD, Barber AE, Heins BM, Svendsen CN. Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington’s disease. Exp Neurol 2010, 224: 155–162.PubMedCrossRefGoogle Scholar
  58. [58]
    McBride JL, Ramaswamy S, Gasmi M, Bartus RT, Herzog CD, Brandon EP, et al. Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 2006, 103: 9345–9350.PubMedCrossRefGoogle Scholar
  59. [59]
    Althaus HH. Remyelination in multiple sclerosis: a new role for neurotrophins? Prog Brain Res 2004, 146: 415–432.PubMedCrossRefGoogle Scholar
  60. [60]
    De Santi L, Annunziata P, Sessa E, Bramanti P. Brain-derived neurotrophic factor and TrkB receptor in experimental autoimmune encephalomyelitis and multiple sclerosis. J Neurol Sci 2009, 287: 17–26.PubMedCrossRefGoogle Scholar
  61. [61]
    Marriott MP, Emery B, Cate HS, Binder MD, Kemper D, Wu Q, et al. Leukemia inhibitory factor signaling modulates both central nervous system demyelination and myelin repair. Glia 2008, 56: 686–698.PubMedCrossRefGoogle Scholar
  62. [62]
    Jones JL, Anderson JM, Phuah CL, Fox EJ, Selmaj K, Margolin D, et al. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain 2010, 133: 2232–2247.PubMedCrossRefGoogle Scholar
  63. [63]
    Ebadi M, Bashir RM, Heidrick ML, Hamada FM, Refaey HE, Hamed A, et al. Neurotrophins and their receptors in nerve injury and repair. Neurochem Int 1997, 30: 347–374.PubMedCrossRefGoogle Scholar
  64. [64]
    Linker RA, Lee DH, Demir S, Wiese S, Kruse N, Siglienti I, et al. Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain 2010, 133: 2248–2263.PubMedCrossRefGoogle Scholar
  65. [65]
    Melli G, Hoke A. Canadian Association of Neurosciences review: regulation of myelination by trophic factors and neuron-glial signaling. Can J Neurol Sci 2007, 34: 288–295.PubMedGoogle Scholar
  66. [66]
    Ubhi K, Rockenstein E, Mante M, Inglis C, Adame A, Patrick C, et al. Neurodegeneration in a transgenic mouse model of multiple system atrophy is associated with altered expression of oligodendroglial-derived neurotrophic factors. J Neurosci 2010, 30: 6236–6246.PubMedCrossRefGoogle Scholar
  67. [67]
    Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA, et al. LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nat Med 2002, 8: 613–619.PubMedCrossRefGoogle Scholar
  68. [68]
    Knapp PE, Adams MH. Epidermal growth factor promotes oligodendrocyte process formation and regrowth after injury. Exp Cell Res 2004, 296: 135–144.PubMedCrossRefGoogle Scholar
  69. [69]
    Lee DH, Geyer E, Flach AC, Jung K, Gold R, Flügel A, et al. Central nervous system rather than immune cellderived BDNF mediates axonal protective effects early in autoimmune demyelination. Acta Neuropathol 2012, 123: 247–258.PubMedCrossRefGoogle Scholar
  70. [70]
    Tabakman R, Lecht S, Sephanova S, Arien-Zakay H, Lazarovici P. Interactions between the cells of the immune and nervous system: neurotrophins as neuroprotection mediators in CNS injury. Prog Brain Res 2004, 146: 387–401.PubMedGoogle Scholar
  71. [71]
    Gudi V, Skuljec J, Yildiz O, Frichert K, Skripuletz T, Moharregh-Khiabani D, et al. Spatial and temporal profiles of growth factor expression during CNS demyelination reveal the dynamics of repair priming. PLoS One 2011, 6: e22623.PubMedCrossRefGoogle Scholar
  72. [72]
    Butzkueven H, Emery B, Cipriani T, Marriott MP, Kilpatrick TJ. Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss. Glia 2006, 53: 696–703.PubMedCrossRefGoogle Scholar
  73. [73]
    Zhu W, Frost EE, Begum F, Vora P, Au K, Gong Y, et al. The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis. J Cell Mol Med 2012, 16: 1856–1865.PubMedCrossRefGoogle Scholar
  74. [74]
    Laudiero LB, Aloe L, Levi-Montalcini R, Buttinelli C, Schilter D, Gillessen S, et al. Multiple sclerosis patients express increased levels of beta-nerve growth factor in cerebrospinal fluid. Neurosci Lett 1992, 147: 9–12.PubMedCrossRefGoogle Scholar
  75. [75]
    Gonzalez-Perez O, Romero-Rodriguez R, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem Cells 2009, 27: 2032–2043.PubMedCrossRefGoogle Scholar
  76. [76]
    Aguirre A, Dupree JL, Mangin JM, Gallo V. A functional role for EGFR signaling in myelination and remyelination. Nat Neurosci 2007, 10: 990–1002.PubMedCrossRefGoogle Scholar
  77. [77]
    Baj G, Leone E, Chao MV, Tongiorgi E. Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments. Proc Natl Acad Sci U S A 2011, 108: 16813–16818.PubMedCrossRefGoogle Scholar
  78. [78]
    Chiaruttini C, Sonego M, Baj G, Simonato M, Tongiorgi E. BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae. Mol Cell Neurosci 2008, 37: 11–19.PubMedCrossRefGoogle Scholar
  79. [79]
    Greenberg ME, Xu B, Lu B, Hempstead BL. New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci 2009, 29: 12764–12767.PubMedCrossRefGoogle Scholar
  80. [80]
    Metsis M, Timmusk T, Arenas E, Persson H. Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain following neuronal activation. Proc Natl Acad Sci U S A 1993, 90: 8802–8806.PubMedCrossRefGoogle Scholar
  81. [81]
    Aid T, Kazantseva A, Piirsoo M, Palm K, Timmusk T. Mouse and rat BDNF gene structure and expression revisited. J Neurosci Res 2007, 85: 525–535.PubMedCrossRefGoogle Scholar
  82. [82]
    Lau AG, Irier HA, Gu J, Tian D, Ku L, Liu G, et al. Distinct 3’UTRs differentially regulate activity-dependent translation of brain-derived neurotrophic factor (BDNF). Proc Natl Acad Sci U S A 2010, 107: 15945–15950.PubMedCrossRefGoogle Scholar
  83. [83]
    Yamakuni H, Kawaguchi N, Ohtani Y, Nakamura J, Katayama T, Nakagawa T, et al. ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes. J Neuroimmunol 2002, 129: 43–50.PubMedCrossRefGoogle Scholar
  84. [84]
    Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, et al. Astrocytes promote myelination in response to electrical impulses. Neuron 2006, 49: 823–832.PubMedCrossRefGoogle Scholar
  85. [85]
    Deverman BE, Patterson PH. Exogenous leukemia inhibitory factor stimulates oligodendrocyte progenitor cell proliferation and enhances hippocampal remyelination. J Neurosci 2012, 32: 2100–2109.PubMedCrossRefGoogle Scholar
  86. [86]
    Marmur R, Kessler JA, Zhu G, Gokhan S, Mehler MF. Differentiation of oligodendroglial progenitors derived from cortical multipotent cells requires extrinsic signals including activation of gp130/LIFbeta receptors. J Neurosci 1998, 18: 9800–9811.PubMedGoogle Scholar
  87. [87]
    Lee DA, Zurawel RH, Windebank AJ. Ciliary neurotrophic factor expression in Schwann cells is induced by axonal contact. J Neurochem 1995, 65: 564–568.PubMedCrossRefGoogle Scholar
  88. [88]
    Stockli KA, Lillien LE, Naher-Noe M, Breitfeld G, Hughes RA, Raff MC, et al. Regional distribution, developmental changes, and cellular localization of CNTF-mRNA and protein in the rat brain. J Cell Biol 1991, 115: 447–459.PubMedCrossRefGoogle Scholar
  89. [89]
    Rivera FJ, Kandasamy M, Couillard-Despres S, Caioni M, Sanchez R, Huber C, et al. Oligodendrogenesis of adult neural progenitors: differential effects of ciliary neurotrophic factor and mesenchymal stem cell derived factors. J Neurochem 2008, 107: 832–843.PubMedCrossRefGoogle Scholar
  90. [90]
    Cao Q, He Q, Wang Y, Cheng X, Howard RM, Zhang Y, et al. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury. J Neurosci 2010, 30: 2989–3001.PubMedCrossRefGoogle Scholar
  91. [91]
    Kelleher MO, Myles LM, Al-Abri RK, Glasby MA. The use of ciliary neurotrophic factor to promote recovery after peripheral nerve injury by delivering it at the site of the cell body. Acta Neurochir 2006, 148: 55–60; discussion 60–51.PubMedCrossRefGoogle Scholar
  92. [92]
    Kang SS, Keasey MP, Cai J, Hagg T. Loss of neuronastroglial interaction rapidly induces protective CNTF expression after stroke in mice. J Neurosci 2012, 32: 9277–9287.PubMedCrossRefGoogle Scholar
  93. [93]
    Gold BT, Johnson NF, Powell DK, Smith CD. White matter integrity and vulnerability to Alzheimer’s disease: Preliminary findings and future directions. Biochim Biophys Acta 2012, 1822: 416–422.PubMedCrossRefGoogle Scholar
  94. [94]
    Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM, et al. Diffusion tensor imaging in presymptomatic and early Huntington’s disease: Selective white matter pathology and its relationship to clinical measures. Mov Disord 2006, 21: 1317–1325.PubMedCrossRefGoogle Scholar
  95. [95]
    Di Paola M, Luders E, Cherubini A, Sanchez-Castaneda C, Thompson PM, Toga AW, et al. Multimodal MRI analysis of the corpus callosum reveals white matter differences in presymptomatic and early Huntington’s disease. Cereb Cortex 2012, 22: 2858–2866.PubMedCrossRefGoogle Scholar
  96. [96]
    Bohnen NI, Albin RL. White matter lesions in Parkinson disease. Nat Rev Neurol 2011, 7: 229–236.PubMedCrossRefGoogle Scholar
  97. [97]
    Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimer disease. Acta Neuropathol 2009, 118: 5–36.PubMedCrossRefGoogle Scholar
  98. [98]
    Zheng Z, Diamond MI. Huntington Disease and the huntingtin protein. Prog in Mol Biol Transl Sci 2012, 107: 189–214.CrossRefGoogle Scholar
  99. [99]
    Jellinger KA. Neuropathology of sporadic Parkinson’s disease: Evaluation and changes of concepts. Mov Disord 2012, 27: 8–30.PubMedCrossRefGoogle Scholar
  100. [100]
    Alberch J, Perez-Navarro E, Canals JM. Neurotrophic factors in Huntington’s disease. Prog Brain Res 2004, 146: 195–229.PubMedGoogle Scholar
  101. [101]
    Pezet S, Malcangio M. Brain-derived neurotrophic factor as a drug target for CNS disorders. Expert Opin Ther Targets 2004, 8: 391–399.PubMedCrossRefGoogle Scholar
  102. [102]
    Lu PH, Lee GJ, Tishler TA, Meghpara M, Thompson PM, Bartzokis G. Myelin breakdown mediates age-related slowing in cognitive processing speed in healthy elderly men. Brain Cogn 2013, 81: 131–138.PubMedCrossRefGoogle Scholar
  103. [103]
    Roth AD, Ramirez G, Alarcon R, Von Benhardi R. Oligodendrocytes damage in Alzheimer’s disease: Beta amyloid toxicity and inflammation. Biol Res 2005, 38: 381–387.PubMedCrossRefGoogle Scholar
  104. [104]
    Jantaratnotai N, Ryu JK, Kim SU, McLarnon JG. Amyloid [beta]_peptide-induced corpus callosum damage and glial activation in vivo. NeuroReport 2003, 14: 1429–1433.PubMedCrossRefGoogle Scholar
  105. [105]
    Desai MK, Guercio BJ, Narrow WC, Bowers WJ. An Alzheimer’s disease-relevant presenilin-1 mutation augments amyloid-beta-induced oligodendrocyte dysfunction. Glia 2011, 59: 627–640.PubMedCrossRefGoogle Scholar
  106. [106]
    Desai MK, Sudol KL, Janelsins MC, Mastrangelo MA, Frazer ME, Bowers WJ. Triple-transgenic Alzheimer’s disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology. Glia 2009, 57: 54–65.PubMedCrossRefGoogle Scholar
  107. [107]
    Desai MK, Mastrangelo MA, Ryan DA, Sudol KL, Narrow WC, Bowers WJ. Early oligodendrocyte/myelin pathology in Alzheimer’s disease mice constitutes a novel therapeutic target. Am J Pathol 2010, 177: 1422–1435.PubMedCrossRefGoogle Scholar
  108. [108]
    Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 2005, 171: 1001–1012.PubMedCrossRefGoogle Scholar
  109. [109]
    Hsiao H-Y, Chern Y. Targeting glial cells to elucidate the pathogenesis of Huntington’s disease. Mol Neurobiol 2010, 41: 248–255.PubMedCrossRefGoogle Scholar
  110. [110]
    Bradford J, Shin JY, Roberts M, Wang CE, Li XJ, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A 2009, 106: 22480–22485.PubMedCrossRefGoogle Scholar
  111. [111]
    Ciarmiello A, Cannella M, Lastoria S, Simonelli M, Frati L, Rubinsztein DC, et al. Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington’s disease. J Nucl Med 2006, 47: 215–222.PubMedGoogle Scholar
  112. [112]
    Beglinger LJ, Nopoulos PC, Jorge RE, Langbehn DR, Mikos AE, Moser DJ, et al. White matter volume and cognitive dysfunction in early Huntington’s disease. Cogn Behav Neurol 2005, 18: 102–107.PubMedCrossRefGoogle Scholar
  113. [113]
    Bartzokis G, Lu P, Tishler T, Fong S, Oluwadara B, Finn JP, et al. Myelin breakdown and iron changes in Huntington’s disease: pathogenesis and treatment implications. Neurochem Res 2007, 32: 1655–1664.PubMedCrossRefGoogle Scholar
  114. [114]
    Myers RH, Vonsattel JP, Paskevich PA, Kiely DK, Stevens TJ, Cupples LA, et al. Decreased neuronal and increased oligodendroglial densities in Huntington’s disease caudate nucleus. J Neuropathol Exp Neurol 1991, 50: 729–742.PubMedCrossRefGoogle Scholar
  115. [115]
    Gómez-Tortosa E, MacDonald ME, Friend JC, Taylor SAM, Weiler LJ, Cupples LA, et al. Quantitative neuropathological changes in presymptomatic Huntington’s disease. Ann Neurol 2001, 49: 29–34.PubMedCrossRefGoogle Scholar
  116. [116]
    Halliday GM, Stevens CH. Glia: Initiators and progressors of pathology in Parkinson’s disease. Mov Disord 2011, 26: 6–17.PubMedCrossRefGoogle Scholar
  117. [117]
    Arai T, Uéda K, Ikeda K, Akiyama H, Haga C, Kondo H, et al. Argyrophilic glial inclusions in the midbrain of patients with Parkinson’s disease and diffuse Lewy body disease are immunopositive for NACP/α-synuclein. Neurosci Lett 1999, 259: 83–86.PubMedCrossRefGoogle Scholar
  118. [118]
    Wakabayashi K, Hayashi S, Yoshimoto M, Kudo H, Takahashi H. NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol 2000, 99: 14–20.PubMedCrossRefGoogle Scholar
  119. [119]
    Braak H, Del Tredici K. Poor and protracted myelination as a contributory factor to neurodegenerative disorders. Neurobiol Aging 2004, 25: 19–23.PubMedCrossRefGoogle Scholar
  120. [120]
    Braak H, Del Tredici K. Neuroanatomy and pathology of sporadic Parkinson’s disease. Adv Anat Embryol Cell Biol 2009, 201: 1–119.PubMedGoogle Scholar
  121. [121]
    Yamada T, McGeer PL, McGeer EG. Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol 1992, 84: 100–104.PubMedCrossRefGoogle Scholar
  122. [122]
    Ahmed Z, Asi YT, Sailer A, Lees AJ, Houlden H, Revesz T, et al. The neuropathology, pathophysiology and genetics of multiple system atrophy. Neuropathol Appl Neurobiol 2012, 38: 4–24.PubMedCrossRefGoogle Scholar
  123. [123]
    Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. Lancet Neurol 2009, 8: 1172–1178.PubMedCrossRefGoogle Scholar
  124. [124]
    Wenning GK, Stefanova N, Jellinger KA, Poewe W, Schlossmacher MG. Multiple system atrophy: A primary oligodendrogliopathy. Ann Neurol 2008, 64: 239–246.PubMedCrossRefGoogle Scholar
  125. [125]
    Stefanova N, Schanda K, Klimaschewski L, Poewe W, Wenning GK, Reindl M. Tumor necrosis factor-α-induced cell death in U373 cells overexpressing α-synuclein. J Neurosci Res 2003, 73: 334–340.PubMedCrossRefGoogle Scholar
  126. [126]
    Riedel M, Goldbaum O, Richter-Landsberg C. α-Synuclein promotes the recruitment of tau to protein inclusions in oligodendroglial cells: effects of oxidative and proteolytic stress. J Mol Neurosci 2009, 39: 226–234.PubMedCrossRefGoogle Scholar
  127. [127]
    Stefanova N, Reindl M, Neumann M, Haass C, Poewe W, Kahle PJ, et al. Oxidative stress in transgenic mice with oligodendroglial α-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol 2005, 166: 869–876.PubMedCrossRefGoogle Scholar
  128. [128]
    Hasegawa T, Baba T, Kobayashi M, Konno M, Sugeno N, Kikuchi A, et al. Role of TPPP/p25 on α-synuclein-mediated oligodendroglial degeneration and the protective effect of SIRT2 inhibition in a cellular model of multiple system atrophy. Neurochem Int 2010, 57: 857–866.PubMedCrossRefGoogle Scholar
  129. [129]
    Kragh CL, Lund LB, Febbraro F, Hansen HD, Gai WP, El-Agnaf O, et al. α-Synuclein aggregation and Ser-129 phosphorylation-dependent cell death in oligodendroglial cells. J Biol Chem 2009, 284: 10211–10222.PubMedCrossRefGoogle Scholar
  130. [130]
    Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Spooren W, et al. Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 2002, 3: 583–588.PubMedCrossRefGoogle Scholar
  131. [131]
    Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, et al. Mouse model of multiple system atrophy alphasynuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 2005, 45: 847–859.PubMedCrossRefGoogle Scholar
  132. [132]
    Shults CW, Rockenstein E, Crews L, Adame A, Mante M, Larrea G, et al. Neurological and neurodegenerative alterations in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: Implications for multiple system atrophy. J Neurosci 2005, 25: 10689–10699.PubMedCrossRefGoogle Scholar
  133. [133]
    Ubhi K, Rockenstein E, Mante M, Inglis C, Adame A, Patrick C, et al. Neurodegeneration in a transgenic mouse model of multiple system atrophy is associated with altered expression of oligodendroglial-derived neurotrophic factors. J Neurosci 2010, 30: 6236–6246.PubMedCrossRefGoogle Scholar
  134. [134]
    Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 2012, 487: 443–448.PubMedCrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Andrew N. Bankston
    • 1
  • Mariana D. Mandler
    • 1
  • Yue Feng
    • 1
  1. 1.Department of PharmacologyEmory University School of MedicineAtlantaUSA

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