Oligodendrocytes: Functioning in a Delicate Balance Between High Metabolic Requirements and Oxidative Damage

  • Alejandro D. RothEmail author
  • Marco T. Núñez
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 949)


The study of the metabolic interactions between myelinating glia and the axons they ensheath has blossomed into an area of research much akin to the elucidation of the role of astrocytes in tripartite synapses (Tsacopoulos and Magistretti in J Neurosci 16:877–885, 1996). Still, unlike astrocytes, rich in cytochrome-P450 and other anti-oxidative defense mechanisms (Minn et al. in Brain Res Brain Res Rev 16:65–82, 1991; Wilson in Can J Physiol Pharmacol. 75:1149–1163, 1997), oligodendrocytes can be easily damaged and are particularly sensitive to both hypoxia and oxidative stress, especially during their terminal differentiation phase and while generating myelin sheaths. In the present review, we will focus in the metabolic complexity of oligodendrocytes, particularly during the processes of differentiation and myelin deposition, and with a specific emphasis in the context of oxidative stress and the intricacies of the iron metabolism of the most iron-loaded cells of the central nervous system (CNS).


Myelination Ensheathment Reactive oxygen species (ROS) Oligodendrocyte precursor cells (OPCs) 



This work was made possible in part by grant PIA-CONICYT ACT1114 and a support grant 2014 from the Faculty of Science of the University of Chile.


  1. Aggarwal S, Yurlova L, Simons M (2011) Central nervous system myelin: structure, synthesis and assembly. Trends Cell Biol 21:585–593PubMedCrossRefGoogle Scholar
  2. Alcazar A, Cid C (2009) High cytotoxic sensitivity of the oligodendrocyte precursor cells to HSP90 inhibitors in cell cultures. Exp Neurol 216:511–514PubMedCrossRefGoogle Scholar
  3. Arosio P, Levi S (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 1800:783–792PubMedCrossRefGoogle Scholar
  4. Baarine M, Andreoletti P, Athias A, Nury T, Zarrouk A, Ragot K, Vejux A, Riedinger JM, Kattan Z, Bessede G, Trompier D, Savary S, Cherkaoui-Malki M, Lizard G (2012) Evidence of oxidative stress in very long chain fatty acid–treated oligodendrocytes and potentialization of ROS production using RNA interference-directed knockdown of ABCD1 and ACOX1 peroxisomal proteins. Neuroscience 213:1–18PubMedCrossRefGoogle Scholar
  5. Back SA, Gan X, Li Y, Rosenberg PA, Volpe JJ (1998) Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci 18:6241–6253PubMedGoogle Scholar
  6. Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC (2001) Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci 21:1302–1312PubMedGoogle Scholar
  7. Back SA, Luo NL, Mallinson RA, O’Malley JP, Wallen LD, Frei B, Morrow JD, Petito CK, Roberts CT Jr, Murdoch GH, Montine TJ (2005) Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes. Ann Neurol 58:108–120PubMedCrossRefGoogle Scholar
  8. Badaracco ME, Siri MV, Pasquini JM (2010) Oligodendrogenesis: the role of iron. BioFactors 36:98–102PubMedGoogle Scholar
  9. Baes M, Aubourg P (2009) Peroxisomes, myelination, and axonal integrity in the CNS. Neuroscientist 15:367–379PubMedCrossRefGoogle Scholar
  10. Barbarese E, Pfeiffer SE (1981) Developmental regulation of myelin basic protein in dispersed cultures. Proc Natl Acad Sci USA 78:1953–1957PubMedPubMedCentralCrossRefGoogle Scholar
  11. Barres BA, Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992) Cell death in the oligodendrocyte lineage. J Neurobiol 23:1221–1230PubMedCrossRefGoogle Scholar
  12. Barres BA, Jacobson MD, Schmid R, Sendtner M, Raff MC (1993) Does oligodendrocyte survival depend on axons? Curr Biol 3:489–497PubMedCrossRefGoogle Scholar
  13. Bauer NG, Richter-Landsberg C, Ffrench-Constant C (2009) Role of the oligodendroglial cytoskeleton in differentiation and myelination. Glia 57:1691–1705Google Scholar
  14. Baumann N, Pham-Dinh D (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 81:871–927PubMedGoogle Scholar
  15. Beard JL, Connor JR (2003) Iron status and neural functioning. Annu Rev Nutr 23:41–58PubMedCrossRefGoogle Scholar
  16. Benkovic SA, Connor JR (1993) Ferritin, transferrin, and iron in selected regions of the adult and aged rat brain. J Comp Neurol 338:97–113PubMedCrossRefGoogle Scholar
  17. Brown AM, Wender R, Ransom BR (2001) Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 66:839–843PubMedCrossRefGoogle Scholar
  18. Burdo JR, Menzies SL, Simpson IA, Garrick LM, Garrick MD, Dolan KG, Haile DJ, Beard JL, Connor JR (2001) Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. J Neurosci Res 66:1198–1207PubMedCrossRefGoogle Scholar
  19. Chrast R, Saher G, Nave KA, Verheijen MH (2011) Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models. J Lipid Res 52:419–434PubMedPubMedCentralCrossRefGoogle Scholar
  20. Connor JR, Menzies SL (1995) Cellular management of iron in the brain. J Neurol Sci 134(Suppl):33–44PubMedCrossRefGoogle Scholar
  21. Connor JR, Menzies SL (1996) Relationship of iron to oligodendrocytes and myelination. Glia 17:83–93PubMedCrossRefGoogle Scholar
  22. Court FA, Hendriks WT, Macgillavry HD, Alvarez J, van Minnen J (2008) Schwann cell to axon transfer of ribosomes: toward a novel understanding of the role of glia in the nervous system. J Neurosci 28:11024–11029PubMedCrossRefGoogle Scholar
  23. Dammann O, Leviton A (2004) Inflammatory brain damage in preterm newborns-dry numbers, wet lab, and causal inferences. Early Hum Dev 79:1–15PubMedCrossRefGoogle Scholar
  24. Dhaunchak AS, Huang JK, De Faria O Jr, Roth AD, Pedraza L, Antel JP, Bar-Or A, Colman DR (2010) A proteome map of axoglial specializations isolated and purified from human central nervous system. Glia 58:1949–1960PubMedCrossRefGoogle Scholar
  25. Dwork AJ, Schon EA, Herbert J (1988) Nonidentical distribution of transferrin and ferric iron in human brain. Neuroscience 27:333–345PubMedCrossRefGoogle Scholar
  26. Edwards AD, Tan S (2006) Perinatal infections, prematurity and brain injury. Curr Opin Pediatr 18:119–124PubMedCrossRefGoogle Scholar
  27. El Waly B, Macchi M, Cayre M, Durbec P (2014) Oligodendrogenesis in the normal and pathological central nervous system. Front Neurosci 8:145PubMedPubMedCentralGoogle Scholar
  28. Erb GL, Osterbur DL, LeVine SM (1996) The distribution of iron in the brain: a phylogenetic analysis using iron histochemistry. Brain Res Dev Brain Res 93:120–128PubMedCrossRefGoogle Scholar
  29. Espinosa de los Monteros A, Foucaud B (1987) Effect of iron and transferrin on pure oligodendrocytes in culture; characterization of a high-affinity transferrin receptor at different ages. Brain Res 432:123–130Google Scholar
  30. Espinosa-Jeffrey A, Wakeman DR, Kim SU, Snyder EY, de Vellis J (2009) Culture system for rodent and human oligodendrocyte specification, lineage progression, and maturation. Curr Protoc Stem Cell Biol Chapter 2:Unit 2D.4Google Scholar
  31. Felt BT, Beard JL, Schallert T, Shao J, Aldridge JW, Connor JR, Georgieff MK, Lozoff B (2006) Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats. Behav Brain Res 171:261–270PubMedPubMedCentralCrossRefGoogle Scholar
  32. Ffrench-Constant C, Colognato H, Franklin RJ (2004) Neuroscience. The mysteries of myelin unwrapped. Science 304:688–689 Google Scholar
  33. Foran DR, Peterson AC (1992) Myelin acquisition in the central nervous system of the mouse revealed by an MBP-Lac Z transgene. J Neurosci 12:4890–4897PubMedGoogle Scholar
  34. French HM, Reid M, Mamontov P, Simmons RA, Grinspan JB (2009) Oxidative stress disrupts oligodendrocyte maturation. J Neurosci Res 87:3076–3087PubMedPubMedCentralCrossRefGoogle Scholar
  35. Funfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brinkmann BG, Kassmann CM, Tzvetanova ID, Mobius W, Diaz F, Meijer D, Suter U, Hamprecht B, Sereda MW, Moraes CT, Frahm J, Goebbels S, Nave KA (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517–521PubMedPubMedCentralGoogle Scholar
  36. Giometto B, Bozza F, Argentiero V, Gallo P, Pagni S, Piccinno MG, Tavolato B (1990) Transferrin receptors in rat central nervous system. An immunocytochemical study. J Neurol Sci 98:81–90PubMedCrossRefGoogle Scholar
  37. Gopalakrishnan G, Awasthi A, Belkaid W, De Faria O Jr, Liazoghli D, Colman DR, Dhaunchak AS (2013) Lipidome and proteome map of myelin membranes. J Neurosci Res 91:321–334PubMedCrossRefGoogle Scholar
  38. Grantham-McGregor S, Ani C (2001) A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 131:649S–666S; discussion 666S–668SGoogle Scholar
  39. Greisen G, Borch K (2001) White matter injury in the preterm neonate: the role of perfusion. Dev Neurosci 23:209–212PubMedCrossRefGoogle Scholar
  40. Guan JZ, Guan WP, Maeda T, Guoqing X, GuangZhi W, Makino N (2014) Patients with multiple sclerosis show increased oxidative stress markers and somatic telomere length shortening. Mol Cell Biochem 400:183–187PubMedCrossRefGoogle Scholar
  41. Guardia Clausi M, Pasquini LA, Soto EF, Pasquini JM (2010) Apotransferrin-induced recovery after hypoxic/ischaemic injury on myelination. ASN Neuro 2:e00048PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hametner S, Wimmer I, Haider L, Pfeifenbring S, Bruck W, Lassmann H (2013) Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol 74:848–861PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hartline DK, Colman DR (2007) Rapid conduction and the evolution of giant axons and myelinated fibers. Curr Biol 17:R29–R35PubMedCrossRefGoogle Scholar
  44. Haynes RL, van Leyen K (2013) 12/15-lipoxygenase expression is increased in oligodendrocytes and microglia of periventricular leukomalacia. Dev Neurosci 35:140–154PubMedGoogle Scholar
  45. Hill JM, Ruff MR, Weber RJ, Pert CB (1985) Transferrin receptors in rat brain: neuropeptide-like pattern and relationship to iron distribution. Proc Natl Acad Sci USA 82:4553–4557PubMedPubMedCentralCrossRefGoogle Scholar
  46. Hirrlinger J, Nave KA (2014) Adapting brain metabolism to myelination and long-range signal transduction. Glia 62:1749–1761PubMedCrossRefGoogle Scholar
  47. Hu Y, Chen G, Wan H, Zhang Z, Zhi H, Liu W, Qian X, Chen M, Wen L, Gao F, Li J, Zhao L (2013) A rat pup model of cerebral palsy induced by prenatal inflammation and hypoxia. Neural Regen Res 8:817–824PubMedPubMedCentralGoogle Scholar
  48. Hulet SW, Heyliger SO, Powers S, Connor JR (2000) Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. J Neurosci Res 61:52–60PubMedCrossRefGoogle Scholar
  49. Ishii A, Dutta R, Wark GM, Hwang SI, Han DK, Trapp BD, Pfeiffer SE, Bansal R (2009) Human myelin proteome and comparative analysis with mouse myelin. Proc Natl Acad Sci USA 106:14605–14610PubMedPubMedCentralCrossRefGoogle Scholar
  50. Jahn O, Tenzer S, Werner HB (2009) Myelin proteomics: molecular anatomy of an insulating sheath. Mol Neurobiol 40:55–72PubMedPubMedCentralCrossRefGoogle Scholar
  51. Jarjour AA, Manitt C, Moore SW, Thompson KM, Yuh SJ, Kennedy TE (2003) Netrin-1 is a chemorepellent for oligodendrocyte precursor cells in the embryonic spinal cord. J Neurosci 23:3735–3744PubMedGoogle Scholar
  52. Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9:173–179PubMedCrossRefGoogle Scholar
  53. Khwaja O, Volpe JJ (2008) Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 93:F153–F161PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kramer EM, Schardt A, Nave KA (2001) Membrane traffic in myelinating oligodendrocytes. Microsc Res Tech 52:656–671PubMedCrossRefGoogle Scholar
  55. Kretchmer N, Beard JL, Carlson S (1996) The role of nutrition in the development of normal cognition. Am J Clin Nutr 63:997S–1001SPubMedGoogle Scholar
  56. LeVine SM (1997) Iron deposits in multiple sclerosis and Alzheimer’s disease brains. Brain Res 760:298–303PubMedCrossRefGoogle Scholar
  57. LeVine SM, Macklin WB (1990) Iron-enriched oligodendrocytes: a reexamination of their spatial distribution. J Neurosci Res 26:508–512PubMedCrossRefGoogle Scholar
  58. Li Y, Guan Q, Chen Y, Han H, Liu W, Nie Z (2013) Transferrin receptor and ferritin-H are developmentally regulated in oligodendrocyte lineage cells. Neural Regen Res 8:6–12PubMedPubMedCentralCrossRefGoogle Scholar
  59. Lozoff B, Wolf AW, Jimenez E (1996) Iron-deficiency anemia and infant development: effects of extended oral iron therapy. J Pediatr 129:382–389PubMedCrossRefGoogle Scholar
  60. Matute C, Alberdi E, Domercq M, Sanchez-Gomez MV, Perez-Samartin A, Rodriguez-Antigüedad A, Perez-Cerda F (2007) Excitotoxic damage to white matter. J Anat 210:693–702PubMedPubMedCentralCrossRefGoogle Scholar
  61. Mehlhase J, Gieche J, Widmer R, Grune T (2006) Ferritin levels in microglia depend upon activation: modulation by reactive oxygen species. Biochim Biophys Acta 1763:854–859PubMedCrossRefGoogle Scholar
  62. Miller RH, Mi S (2007) Dissecting demyelination. Nat Neurosci 10:1351–1354PubMedCrossRefGoogle Scholar
  63. Minn A, Ghersi-Egea JF, Perrin R, Leininger B, Siest G (1991) Drug metabolizing enzymes in the brain and cerebral microvessels. Brain Res Brain Res Rev 16:65–82PubMedCrossRefGoogle Scholar
  64. Mir F, Lee D, Ray H, Sadiq SA (2014) CSF isoprostane levels are a biomarker of oxidative stress in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 1:e21PubMedPubMedCentralCrossRefGoogle Scholar
  65. Morland C, Henjum S, Iversen EG, Skrede KK, Hassel B (2007) Evidence for a higher glycolytic than oxidative metabolic activity in white matter of rat brain. Neurochem Int 50:703–709PubMedCrossRefGoogle Scholar
  66. Nave KA (2010) Myelination and the trophic support of long axons. Nat Rev Neurosci 11:275–283PubMedCrossRefGoogle Scholar
  67. Noble M, Murray K, Stroobant P, Waterfield MD, Riddle P (1988) Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333:560–562PubMedCrossRefGoogle Scholar
  68. Numasawa-Kuroiwa Y, Okada Y, Shibata S, Kishi N, Akamatsu W, Shoji M, Nakanishi A, Oyama M, Osaka H, Inoue K, Takahashi K, Yamanaka S, Kosaki K, Takahashi T, Okano H (2014) Involvement of ER stress in dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 missense mutations shown by iPSC-derived oligodendrocytes. Stem Cell Reports 2:648–661PubMedPubMedCentralCrossRefGoogle Scholar
  69. Nunez MT, Urrutia P, Mena N, Aguirre P, Tapia V, Salazar J (2012) Iron toxicity in neurodegeneration. Biometals 25:761–776PubMedCrossRefGoogle Scholar
  70. Oshiro S, Kawamura K, Zhang C, Sone T, Morioka MS, Kobayashi S, Nakajima K (2008) Microglia and astroglia prevent oxidative stress-induced neuronal cell death: implications for aceruloplasminemia. Biochim Biophys Acta 1782:109–117PubMedCrossRefGoogle Scholar
  71. Oski FA, Honig AS, Helu B, Howanitz P (1983) Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 71:877–880PubMedGoogle Scholar
  72. Pasik P, Pasik T (2004) Cajal, Achúcarro, Río Hortega, and the early exploration of Neuroglia. In: Lazzarini RA (ed) Myelin biology and disorders. Elsevier Academic Press, San Diego, pp xxiii–xliGoogle Scholar
  73. Pedraza L, Huang JK, Colman DR (2001) Organizing principles of the axoglial apparatus. Neuron 30:335–344PubMedCrossRefGoogle Scholar
  74. Pedraza L, Huang JK, Colman D (2009) Disposition of axonal caspr with respect to glial cell membranes: implications for the process of myelination. J Neurosci Res 87:3480–3491PubMedCrossRefGoogle Scholar
  75. Pfeiffer SE, Warrington AE, Bansal R (1993) The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191–197PubMedCrossRefGoogle Scholar
  76. Poliak S, Peles E (2003) The local differentiation of myelinated axons at nodes of Ranvier. Nat Rev Neurosci 4:968–980PubMedCrossRefGoogle Scholar
  77. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24:1037–1047PubMedCrossRefGoogle Scholar
  78. Popko B (2003) Myelin: not just a conduit for conduction. Nat Genet 33:327–328PubMedCrossRefGoogle Scholar
  79. Rasband MN, Trimmer JS, Schwarz TL, Levinson SR, Ellisman MH, Schachner M, Shrager P (1998) Potassium channel distribution, clustering, and function in remyelinating rat axons. J Neurosci 18:36–47PubMedGoogle Scholar
  80. Rosenbluth J (1976) Intramembranous particle distribution at the node of Ranvier and adjacent axolemma in myelinated axons of the frog brain. J Neurocytol 5:731–745PubMedCrossRefGoogle Scholar
  81. Roth AD, Ivanova A, Colman DR (2006) New observations on the compact myelin proteome. Neuron Glia Biol 2:15–21PubMedCrossRefGoogle Scholar
  82. Rowitch DH, Kriegstein AR (2010) Developmental genetics of vertebrate glial-cell specification. Nature 468:214–222PubMedCrossRefGoogle Scholar
  83. Saher G, Brugger B, Lappe-Siefke C, Mobius W, Tozawa R, Wehr MC, Wieland F, Ishibashi S, Nave KA (2005) High cholesterol level is essential for myelin membrane growth. Nat Neurosci 8:468–475PubMedGoogle Scholar
  84. Sauer BM, Schmalstieg WF, Howe CL (2013) Axons are injured by antigen-specific CD8(+) T cells through a MHC class I- and granzyme B-dependent mechanism. Neurobiol Dis 59:194–205PubMedPubMedCentralCrossRefGoogle Scholar
  85. Sbardella E, Greco A, Stromillo ML, Prosperini L, Puopolo M, Cefaro LA, Pantano P, De Stefano N, Minghetti L, Pozzilli C (2013) Isoprostanes in clinically isolated syndrome and early multiple sclerosis as biomarkers of tissue damage and predictors of clinical course. Mult Scler 19:411–417PubMedCrossRefGoogle Scholar
  86. Schulz K, Vulpe CD, Harris LZ, David S (2014) Iron efflux from oligodendrocytes is differentially regulated in gray and white matter. J Neurosci 31:13301–13311CrossRefGoogle Scholar
  87. Silvestroff L, Franco PG, Pasquini JM (2012) ApoTransferrin: dual role on adult subventricular zone-derived neurospheres. PLoS ONE 7:e33937PubMedPubMedCentralCrossRefGoogle Scholar
  88. Silvestroff L, Franco PG, Pasquini JM (2013) Neural and oligodendrocyte progenitor cells: transferrin effects on cell proliferation. ASN Neuro 5:e00107PubMedPubMedCentralCrossRefGoogle Scholar
  89. Simons M, Trotter J (2007) Wrapping it up: the cell biology of myelination. Curr Opin Neurobiol 17:533–540PubMedCrossRefGoogle Scholar
  90. Smith KJ, Kapoor R, Felts PA (1999) Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol 9:69–92PubMedCrossRefGoogle Scholar
  91. Sow A, Lamant M, Bonny JM, Larvaron P, Piaud O, Lecureuil C, Fontaine I, Saleh MC, Garcia Otin AL, Renou JP, Baron B, Zakin M, Guillou F (2006) Oligodendrocyte differentiation is increased in transferrin transgenic mice. J Neurosci Res 83:403–414PubMedCrossRefGoogle Scholar
  92. Stephenson E, Nathoo N, Mahjoub Y, Dunn JF, Yong VW (2014) Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev Neurol 10:459–468PubMedCrossRefGoogle Scholar
  93. Stiefel KM, Torben-Nielsen B, Coggan JS (2013) Proposed evolutionary changes in the role of myelin. Front Neurosci 7:202PubMedPubMedCentralCrossRefGoogle Scholar
  94. Taylor CM, Marta CB, Claycomb RJ, Han DK, Rasband MN, Coetzee T, Pfeiffer SE (2004) Proteomic mapping provides powerful insights into functional myelin biology. Proc Natl Acad Sci USA 101:4643–4648PubMedPubMedCentralCrossRefGoogle Scholar
  95. Todorich B, Zhang X, Slagle-Webb B, Seaman WE, Connor JR (2008) Tim-2 is the receptor for H-ferritin on oligodendrocytes. J Neurochem 107:1495–1505PubMedCrossRefGoogle Scholar
  96. Todorich B, Pasquini JM, Garcia CI, Paez PM, Connor JR (2009) Oligodendrocytes and myelination: the role of iron. Glia 57:467–478PubMedCrossRefGoogle Scholar
  97. Tomassy GS, Fossati V (2014) How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses. Front Cell Neurosci 8:201PubMedPubMedCentralCrossRefGoogle Scholar
  98. Tosic M, Rakic S, Matthieu J, Zecevic N (2002) Identification of Golli and myelin basic proteins in human brain during early development. Glia 37:219–228PubMedCrossRefGoogle Scholar
  99. Toyama BH, Savas JN, Park SK, Harris MS, Ingolia NT, Yates JR 3rd, Hetzer MW (2013) Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell 154:971–982PubMedPubMedCentralCrossRefGoogle Scholar
  100. Traka M, Dupree JL, Popko B, Karagogeos D (2002) The neuronal adhesion protein TAG-1 is expressed by Schwann cells and oligodendrocytes and is localized to the juxtaparanodal region of myelinated fibers. J Neurosci 22:3016–3024PubMedGoogle Scholar
  101. Tsacopoulos M, Magistretti PJ (1996) Metabolic coupling between glia and neurons. J Neurosci 16:877–885PubMedGoogle Scholar
  102. van Meeteren ME, Teunissen CE, Dijkstra CD, van Tol EA (2005) Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr 59:1347–1361PubMedCrossRefGoogle Scholar
  103. Volpe JJ (2001) Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res 50:553–562PubMedCrossRefGoogle Scholar
  104. Volpe JJ, Kinney HC, Jensen FE, Rosenberg PA (2011) The developing oligodendrocyte: key cellular target in brain injury in the premature infant. Int J Dev Neurosci 29:423–440PubMedPubMedCentralCrossRefGoogle Scholar
  105. Wilson JX (1997) Antioxidant defense of the brain: a role for astrocytes. Can J Physiol Pharmacol 75:1149–1163PubMedCrossRefGoogle Scholar
  106. Wilson CH, Hartline DK (2011) Novel organization and development of copepod myelin. ii. nonglial origin. J Comp Neurol 519:3281–3305PubMedCrossRefGoogle Scholar
  107. Xu K, Terakawa S (1999) Fenestration nodes and the wide submyelinic space form the basis for the unusually fast impulse conduction of shrimp myelinated axons. J Exp Biol 202:1979–1989PubMedGoogle Scholar
  108. Yuen TJ, Silbereis JC, Griveau A, Chang SM, Daneman R, Fancy SP, Zahed H, Maltepe E, Rowitch DH (2014) Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis. Cell 158:383–396PubMedPubMedCentralCrossRefGoogle Scholar
  109. Zhang X, Surguladze N, Slagle-Webb B, Cozzi A, Connor JR (2006) Cellular iron status influences the functional relationship between microglia and oligodendrocytes. Glia 54:795–804PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceUniversity of ChileSantiagoChile

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