Open Access Open Access  Restricted Access Subscription or Fee Access

Myelin Ultrastructure Terminology in Disease and Recovery Processes

F. Helvacioglu, A. Dagdeviren

Abstract


Ultrastructural evaluation of myelin coat helps to understand the possible background of pathological changes leading to deterioration or complete loss of nerve functions. A number of terms were previously introduced to describe the fine structural changes in myelin under various conditions. We believe that using a common terminology will be helpful to interpret the structure/function relationship in neurological disorders empowering the diagnosis and possible therapeutical approaches. In this paper, we present examples of ultrastructural changes in myelin during myelination, demyelination, re-myelination and dysmyelination processes and we reviewed the terminology previously used.
We tried to include all studies reporting ultrastructural findings with no limitation to the experimental conditions, the species used and the disorders. The terminology used to describe the structural findings included compacted myelin, partially compacted myelin, noncompacted myelin, redundancy (hypermyelination, tomacula, myelinosome), splitting, complete circular splitting, myelin degradation, concentric lamellar bodies (myelin figures), loss of myelin lamellae, polyaxonal Schwann cells and necrotic cell debris.
Ultrastructural data described in this paper aimed to provide a guide for future studies. We concluded that the evaluation of ultrastructural changes in any neurological disorder is greatly valuable for a better understanding of pathological and physiological changes occured. We also believe that supporting the ultrastructural findings with quantitative methods in the future will be of great value.

Keywords


Schwann cell; myelination; re-myelination; demyelination; dysmyelination; electron microscopy

Full Text:

PDF

References


Arikan M., Togral G., Hasturk AE., Horasanli B., Helvacioglu F., Dagdeviren A., Tekindal M.A., Parpucu M. Histomorphometric and Ultrastructural Evaluation of Long-Term Alpha Lipoic Acid and Vitamin B12 Use After Experimental Sciatic Nerve Injury in Rats. Turk Neurosurg., 26(6): 944-952, 2016.

Bando Y., Nomura T., Bochimoto H., Murakami K., Tanaka T., Watanabe T., Yoshida S. Abnormal morphology of myelin and axon pathology in murine models of multiple sclerosis. Neurochem Int., 81:16-27, 2015.

Cai Z., Blumbergs P.C., Finnie J.W., Manavis J., Thompson .PD. Novel fibroblastic onion bulbs in a demyelinating avian peripheral neuropathy produced by riboflavin deficiency. Acta Neuropathol., 114(2): 187-94, 2007.

Cai Z., Finnie J.W., Blumbergs P.C., Manavis J., Ghabriel M.N., Thompson P.D. Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy. Exp Neurol., 198(1): 65-71, 2006.

Caillaud M., Richard L., Vallat J.M., Desmoulière A., Billet F. Peripheral nerve regeneration and intraneural revascularization. Neural Regen Res., 14(1):24-33, 2019.

Chang K.J., Redmond S.A., Chan J.R. Remodeling myelination: implications for mechanisms of neural plasticity. Nat Neurosci., 19(2):190-7, 2016.

Chomiak T., Hu B. What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach. PLoS One, 4(11): e7754, 2009.

Corfas G., Velardez M.O., Ko C.P., Ratner N., Peles E. Mechanisms and roles of axon-Schwann cell interactions. J Neurosci., 24(42): 9250-60, 2004.

De Robertıs E., Gerschenfeld H.M., Wald F. Cellular mechanism of myelination in the central nervous system. J Biophys Biochem Cytol., 4(5): 651-6, 1958.

Dellon A.L., Mackinnon S.E. Basic scientific and clinical applications of peripheral nerve regeneration. Surg Annu., 20: 59-100, 1988.

Diers A., Kaczinski M., Grohmann K., Hübner C., Stoltenburg-Didinger G.The ultrastructure of peripheral nerve, motor end-plate and skeletal muscle in patients suffering from spinal muscular atrophy with respiratory distress type 1 (SMARD1). Acta Neuropathol., 110(3): 289-97, 2005.

Dupree J.L., Coetzee T., Blight A., Suzuki K., Popko B. Myelin galactolipids are essential for proper node of Ranvier formation in the CNS. J Neurosci.,18(5): 1642-9, 1998.

Eftekharpour E., Karimi-Abdolrezaee S., Wang J., El Beheiry H., Morshead C., Fehlings M.G. Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction. J Neurosci., 27(13): 3416-28, 2007.

Evans G.R. Peripheral nerve injury: a review and approach to tissue engineered constructs. Anat Rec., 263(4):396-404, 2001.

Fancy S.P., Chan J.R., Baranzini S.E., Franklin R.J., Rowitch D.H. Myelin regeneration: a recapitulation of development? Annu Rev Neurosci., 34:21-43, 2011.

Fazal SV, Gomez-Sanchez JA, Wagstaff LJ, Musner N, Otto G, Janz M, Mirsky R, Jessen KR. Graded Elevation of c-Jun in Schwann Cells In Vivo: Gene Dosage Determines Effects on Development, Remyelination, Tumorigenesis, and Hypomyelination. J Neurosci., 37(50): 12297-12313, 2017.

Feltri M.L., Poitelon Y., Previtali S.C. How Schwann Cells Sort Axons: New Concepts. Neuroscientist, 22(3): 252-65, 2016.

Figlia G., Gerber D., Suter U. Myelination and mTOR. Glia, 66(4):693-707, 2018.

Forbes T.A, Gallo V. All Wrapped Up: Environmental Effects on Myelination. Trends. Neurosci., 40(9): 572-587, 2017.

Fraher J. Axons and glial interfaces: ultrastructural studies. J Anat., 200(4): 415-30, 2002.

Freitas M.R., Nascimento O.J., Chimelli L., de Freitas G.R. Charcot-Marie-Tooth disease. Study of sural nerve biopsy in 41 patients. Arq Neuropsiquiatr., 53(3-B): 560-9, 1995.

Helvacioglu F., Kandemir E., Karabacak B., Karatas I., Pecen A., Ercan I., Sencelikel T., Dagdeviren A. Effect of Creatine on Rat Sciatic Nerve Injury: A Comparative Ultrastructural Study. Turk Neurosurg., 28(1): 128-136, 2018.

Hirano A. Review of the morphological aspects of remyelination. Dev Neurosci., 11(2): 112-7, 1989.

Hirano A., Zimmerman H.M., Levine S. Electron microscopic observations of peripheral myelin in a central nervous system lesion. Acta Neuropathol., 12(4): 348-65, 1969.

Ishibashi T., Ding L., Ikenaka K., Inoue Y., Miyado K., Mekada E., Baba H. Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation. J Neurosci., 24(1): 96-102, 2004.

Ishii T., Kawakami E., Endo K., Misawa H., Watabe K. Myelinating cocultures of rodent stem cell line-derived neurons and immortalized Schwann cells. Neuropathology, 37(5): 475-481, 2017.

Kaller M.S., Lazari A., Blanco-Duque C., Sampaio-Baptista C., Johansen-Berg H. Myelin plasticity and behaviour-connecting the dots. Curr Opin Neurobiol., 47: 86-92, 2017.

Kjell J., Olson L. Rat models of spinal cord injury: from pathology to potential therapies. Dis Model Mech., 9(10): 1125-1137, 2016.

Komori T. Pathology of oligodendroglia: An overview. Neuropathology. 37(5): 465-474,2017.

Kotter M.R., Stadelmann C., Hartung H.P. Enhancing remyelination in disease-can we wrap it up? Brain, 134(Pt 7):1882-900, 2011.

Li C., Zhang L., Chao F., Xiao Q., Luo Y., Tang Y. Stereological quantification of age-related changes in myelinated fibers of rat white matter. Neuroreport., 28(1):42-49, 2017.

Lim H., Sharoukhov D., Kassim I., Zhang Y., Salzer J.L., Melendez-Vasquez C.V. Label-free imaging of Schwann cell myelination by third harmonic generation microscopy. Proc Natl Acad Sci., 111(50): 18025-30,2014.

Mitew S., Xing Y.L., Merson T.D. Axonal activity-dependent myelination in development: Insights for myelin repair. J Chem Neuroanat., 76(Pt A): 2-8, 2016.

Möbius W., Nave K.A., Werner H.B. Electron microscopy of myelin: Structure preservation by high-pressure freezing. Brain Res., 1641(Pt A): 92-100, 2016.

Monk K.R., Feltri M.L., Taveggia C. New insights on Schwann cell development. Glia, 63(8): 1376-93, 2015.

Naef R., Suter U. Many facets of the peripheral myelin protein PMP22 in myelination and disease. Microsc Res Tech., 41(5): 359-71, 1998.

Nave K.A., Werner H.B. Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol., 30: 503-33, 2014.

Olmos-Serrano J.L., Kang H.J., Tyler W.A., Silbereis J.C., Cheng F., Zhu Y., Pletikos M., Jankovic-Rapan L., Cramer N.P., Galdzicki Z., Goodliffe J., Peters A., Sethares C., Delalle I.,Golden J.A., Haydar T.F., Sestan N. Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination. Neuron, 89(6): 1208-1222, 2016.

Osorio-Querejeta I., Sáenz-Cuesta M., Muñoz-Culla M., Otaegui D. Models for Studying Myelination, Demyelination and Remyelination. Neuromolecular Med., 19(2-3): 181-192, 2017.

Osso L.A., Chan J.R. Architecting the myelin landscape. Curr Opin Neurobiol., 47: 1-7, 2017.

Otani Y., Yermakov L.M., Dupree J.L., Susuki K. Chronic peripheral nerve compression disrupts paranodal axoglial junctions. Muscle Nerve, 55(4): 544-554, 2017.

Palaniyar N., Semotok J.L., Wood D.D., Moscarello M.A., Harauz G. Human proteolipid protein (PLP) mediates winding and adhesion of phospholipid membranes but prevents their fusion. Biochim Biophys Acta., 1415(1): 85-100, 1998.

Papastefanaki F., Matsas R. From demyelination to remyelination: the road toward therapies for spinal cord injury. Glia, 63(7): 1101-25, 2015.

Patzig J., Kusch K., Fledrich R., Eichel M.A., Lüders K.A., Möbius W., Sereda M.W., Nave K.A., Martini R., Werner H.B. Proteolipid protein modulates preservation of peripheral axons and premature death when myelin protein zero is lacking. Glia. 64(1): 155-74, 2016.

Peters A. The effects of normal aging on myelin and nerve fibers: a review. J Neurocytol., 8-9: 581-93, 2002.

Peters A., Sethares C. Age-related changes in the morphology of cerebral capillaries do not correlate with cognitive decline. J Comp Neurol., 520(6): 1339-47, 2012.

Peters A., Sethares C. Is there remyelination during aging of the primate central nervous system?. J Comp Neurol., 460(2): 238-54, 2003.

Romanelli E., Merkler D., Mezydlo A., Weil M.T., Weber M.S., Nikić I., Potz S., Meinl E., Matznick F.E., Kreutzfeldt M., Ghanem A., Conzelmann K.K., Metz I., Brück W., Routh M., Simons M., Bishop D., Misgeld T., Kerschensteiner M. Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model. Nat Commun., 7: 13275, 2016. doi: 10.1038/ncomms13275.

Saher G., Stumpf S.K. Cholesterol in myelin biogenesis and hypomyelinating disorders. Biochim Biophys Acta., 1851(8):1083-94, 2015.

Saitoh F., Moore S.A., Barresi R., Henry M.D., Messing A., Ross-Barta S.E., Cohn R.D., Williamson R.A., Sluka K.A., Sherman D.L., Brophy P.J., Schmelzer J.D., Low P.A., Wrabetz L., Feltri M.L., Campbell K.P. Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron. 38(5): 747-58, 2003.

Saitoh Y., Ohno N., Yamauchi J., Sakamoto T., Terada N. Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system. Histochem Cell Biol., 148(6): 597-606, 2017.

Salzer J.L. Schwann cell myelination. Cold Spring Harb Perspect Biol., 7(8): a020529, 2015. doi: 10.1101/cshperspect.a020529.

Salzer J.L., Brophy P.J., Peles E. Molecular domains of myelinated axons in the peripheral nervous system. Glia. 56(14): 1532-40, 2008.

Sander S., Ouvrier R.A., McLeod J.G., Nicholson G.A., Pollard J.D. Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies. J Neurol Neurosurg Psychiatry, 68(4): 483-8, 2000.

Seddighi A., Nikouei A., Seddighi A.S., Zali A.R., Tabatabaei S.M., Sheykhi A.R., Yourdkhani F., Naeimian S. Peripheral Nerve Injury: A Review Article. International Clinical Neuroscience Journal, 3 (1): 1-6, 2016.

Seddon H.J. A Classification of Nerve Injuries. Br Med J., 2 (4260): 237-9,1942.

Shen D., Zhang Q., Gao X., Gu X., Ding F. Age-related changes in myelin morphology, electrophysiological property and myelin-associated protein expression of mouse sciatic nerves. Neurosci Lett., 502(3): 162-7, 2011.

Stassart R.M., Möbius W., Nave K.A., Edgar J.M. The Axon-Myelin Unit in Development and Degenerative Disease. Front Neurosci., 12: 467, 2018. doi: 10.3389/fnins.2018.00467. eCollection 2018. Review.

Stolt C.C., Wegner M. Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination. Brain Res., 1641(Pt A): 101-110, 2016.

Sunderland S. A Classification of Peripheral Nerve İnjuries Producing Loss of Function. Brain, 74(4): 491-516, 1951.

Taveggia C. Schwann cells-axon interaction in myelination. Curr Opin Neurobiol., 39: 24-9, 2016.

Tricaud N. Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation. Front Cell Neurosci., 11: 414, 2018.

Uranova N., Orlovskaya D., Vikhreva O., Zimina I., Kolomeets N., Vostrikov V., Rachmanova V. Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull., 55(5): 597-610, 2001.

Vassall K.A., Bamm V.V., Jenkins A.D., Velte C.J., Kattnig D.R., Boggs J.M., Hinderberger D., Harauz G. Substitutions mimicking deimination and phosphorylation of 18.5-kDa myelin basic protein exert local structural effects that subtly influence its global folding. Biochim Biophys Acta., 1858(6): 1262-77, 2016.

Weiskopf N., Mohammadi S., Lutti A., Callaghan M.F. Advances in MRI-based computational neuroanatomy: from morphometry to in-vivo histology. Curr Opin Neurol., 28(4): 313-22, 2015.

White R., Krämer-Albers E.M. Axon-glia interaction and membrane traffic in myelin formation. Front Cell Neurosci., 7: 284-, 2014. doi: 10.3389/fncel.2013.00284

Yi S., Wang Q.H., Zhao L.L., Qin J., Wang Y.X., Yu B., Zhou S.L. miR-30c promotes Schwann cell remyelination following peripheral nerve injury. Neural Regen Res., 12(10): 1708-1715, 2017.

Young P., Boussadia O., Berger P., Leone D.P., Charnay P., Kemler R., Suter U. E-cadherin is required for the correct formation of autotypic adherens junctions of the outer mesaxon but not for the integrity of myelinated fibers of peripheral nerves. Mol Cell Neurosci., 21(2): 341-51, 2002.

Zhou Y., Notterpek L. Promoting peripheral myelin repair. Exp Neurol., 283(Pt B): 573-80, 2016.




DOI: https://doi.org/10.12871/aib.v157i2-3.4697

Refbacks

  • There are currently no refbacks.