DOCSLIB.ORG

Clinical Syndromes Associated with Tomacula Or Myelin Swellings in Sural Nerve Biopsies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Syndromes Associated with Tomacula Or Myelin Swellings in Sural Nerve Biopsies J Neurol Neurosurg Psychiatry 2000;68:483–488 483 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.4.483 on 1 April 2000. Downloaded from Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies S Sander, R A Ouvrier, J G McLeod, G A Nicholson, J D Pollard Abstract syndromes.8–11 Sausage shaped swellings of the Objectives—To describe the neuropatho- myelin sheath were first described by Behse and logical features of clinical syndromes Buchthal in 1972.1 Madrid and Bradley10 subse- associated with tomacula or focal myelin quently gave the name tomaculous neuropathy swellings in sural nerve biospies and to (latin: tomaculum=sausage) and described sev- discuss possible common aetiopathologi- eral mechanisms that may lead to the formation cal pathways leading to their formation in of a tomaculum—for example, hypermyelina- this group of neuropathies. tion, redundant loop formation, the presence of Methods—Fifty two patients with sural a second mesaxon, transnodal myelination, two nerve biopsies reported to show tomacula Schwann cells forming one myelin sheath, and or focal myelin swellings were reviewed, disruption of the myelin sheath. Sural nerve light and electron microscopy were per- biopsies typically show regions of myelin thick- formed, and tomacula were analysed on ening as well as features of demyelination and teased fibre studies. Molecular genetic remyelination. Electrophysiologically, these syn- studies were performed on those patients dromes most often present as multiple monone- who were available for genetic testing. uropathy (sometimes with conduction block) or Results—Thirty seven patients were diag- demyelinating sensorimotor neuropathy. nosed with hereditary neuropathy with In this study we reviewed 52 patients show- liability to pressure palsies (HNPP), four ing myelin swellings on sural nerve biopsy. We with hereditary motor and sensory neu- describe the various clinical syndromes associ- ropathy type I (HMSN I) or Charcot- ated with focal myelin swellings, present their Marie-Tooth disease type 1 (CMT1), four morphological findings, and discuss disease with HMSN with myelin outfolding mechanisms. (CMT4B), three with IgM paraproteine- mic neuropathy, three with chronic in- Materials and methods flammatory demyelinating polyneuro- Samples were obtained by searching sural pathy (CIDP), and one with HMSN III nerve biopsy reports mentioning tomacula or (CMT3). myelin thickenings. The reports were gener- Conclusions—Most of these syndromes ated by three diVerent observers performing were shown to be related to genetic or clinical reports between 1976 and 1998. Each immunological defects of myelin compo- sural nerve biopsy reported to show tomacula http://jnnp.bmj.com/ nents such as peripheral myelin protein 22 or focal myelin swellings on teased fibre studies (PMP22), myelin protein zero (P0), or was subsequently examined. Only myelin myelin associated glycoprotein (MAG). thickenings measuring more than 50% of the These proteins share the HNK-1 epitope fibre diameter were defined as tomacula.12 A which has been implicated in cell adhesion total of 52 sural nerve biopsies were analysed processes. Impaired myelin maintenance by light and electron microscopy. may therefore contribute to the formation of tomacula and subsequent demyelina- HISTOLOGICAL TECHNIQUES on September 29, 2021 by guest. Protected copyright. tion. Sural nerve biopsy was performed according to (J Neurol Neurosurg Psychiatry 2000;68:483–488) standard techniques and prepared for light and electron microscopy as previously described.13 Institute of Clinical Keywords: myelin proteins; peripheral nerves; pathol- Neurosciences, ogy; sural nerve Teased fibres were prepared as described by University of Sydney, Low et al14 and classified according to Dyck et Sydney, NSW 2006, al.15 Australia S Sander The term “tomaculous neuropathy” generally R A Ouvrier refers to hereditary neuropathy with liability to QUANTITATIVE STUDIES JG McLeod pressure palsies (HNPP), which is most com- Diameter and length of tomacula were G A Nicholson monly associated with a deletion of chromo- measured using an ocular micrometer. Twenty J D Pollard some 17p11.2–12 including the peripheral fibres per patient were analysed. Only patients with HNPP carrying a definite molecular diag- Correspondence to: myelin protein 22 (PMP22). Although tomacula 1 Professor John D Pollard, are the pathological hallmark of HNPP focal nosis were included for quantitative analysis. Institute of Clinical thickening of the myelin sheath is also found in Teased fibre preparations of one patient Neurosciences, University of 2 carrying a P0 mutation did not allow quantita- Sydney, NSW 2006, IgM paraproteinemic neuropathy, hereditary Australia motor and sensory neuropathy (HMSN) or tive analysis. Charcot-Marie-Tooth disease (CMT),34 5 Received 26 February 1999 HMSN with myelin outfolding, other forms of MOLECULAR GENETIC TECHNIQUES and in final form 22 November 1999 hereditary neuropathy with myelin outfolding PMP22 deletion, duplication, and mutation Accepted 3 December 1999 or hypermyelination,67 and other clinical analysis was performed as previously 484 Sander, Ouvrier, McLeod, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.4.483 on 1 April 2000. Downloaded from Figure 1 (A) Transverse section of toluidine blue stained epon embedded sural nerve from a patient with HNPP (top arrow, adaxonal myelin breakdown products; bottom arrow, hypermyelinated fibre). (B) Electron micrograph showing a tomaculum with active myelin breakdown. 16 17 described. P0 mutations were analysed MOLECULAR GENETICS according to Bort et al.18 Nineteen patients with HNPP were available for molecular genetic testing. A chromosome Results 17p11.2 deletion was detected in 17 patients, PATIENTS two showed frameshift mutations of the Of 52 patients whose sural nerve biopsies PMP22 gene17 causing a premature stop showed focal myelin swellings, 37 were diag- codon, the result of which is eVectively the nosed with HNPP, four with HMSN type same as a deletion. Two out of four patients 1/CMT1, four with HMSN with myelin with CMT1 underwent genetic testing and outfolding, three with IgM paraproteinaemic showed the typical chromosome 17p11.2 neuropathy and positive anti-MAG antibodies, duplication including the PMP22 gene. A three with chronic inflammatory demyelinating myelin protein zero (P0) point mutation was polyneuropathy (CIDP), and one with HMSN demonstrated in the CMT3 patient. Three out III /CMT3. of four patients with CMT4B were tested for http://jnnp.bmj.com/ on September 29, 2021 by guest. Protected copyright. Figure 2 (A) Transverse section of toluidine blue stained epon embedded sural nerve from a patient with IgM paraproteinemic neuropathy. (B) Electron micrograph showing hypermyelination and redundant loop formation. Clinical syndromes and tomacula or myelin swellings in sural nerve biopsies 485 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.4.483 on 1 April 2000. Downloaded from Figure 3 (A) Transverse section of toluidine blue stained epon embedded sural nerve from a patient with CMT4B (top arrow: fibre with myelin outpouchings; bottom arrow: hypermyelinated fibre with redundant myelin foldings). (B) Electron micrograph showing excessive myelin foldings. P0 and PMP22 gene mutations. In one patient, (fig 1 A) and occasional early onion bulb exons 2, 3, and 4 of the PMP22 gene and exons formations were visible. The average number of 1, 2, 3, and 4 of the P0 gene did not show point myelinated fibres was not greatly reduced. In mutations (exon 1 of the PMP22 gene and the paraproteinaemic neuropathies (fig 2 A) exons 5 and 6 of the P0 gene were not and CIDP the degree of hypermyelination was sequenced). Complete sequence analysis in the less extreme compared with HNPP. By contrast two remaining patients disclosed no mutations with HNPP, in some patients marked fibre loss within the PMP22 nor the P0 gene. was evident. In HMSN with myelin outfolding (fig 3 A) the variation in myelin sheath thickness MORPHOLOGY was most pronounced. Most fibres were very Transverse sections (descriptive data) thinly myelinated, similar to those seen in Light microscopy—In sural nerve biopsies of Dejerine-Sottas syndrome, but there were also patients with HNPP many fibres were found to several fibres showing bizarre formations of be thinly myelinated, some showed profound myelin or many redundant myelin foldings. hypermyelination or redundant myelin foldings Biopsies from patients with HMSN I (CMT1) http://jnnp.bmj.com/ on September 29, 2021 by guest. Protected copyright. Figure 4 (A) Transverse section of toluidine blue stained epon embedded sural nerve from a patient with CMT3 and a P0 mutation showing several onion bulb formations and a fibre with bizarre myelin outfoldings (arrow). (B) Electron micrograph showing bizarre myelin outfoldings. 486 Sander, Ouvrier, McLeod, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.4.483 on 1 April 2000. Downloaded from Table 1 Classification of teased fibres Age (y) A (% fibres) B C,D,F E G Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD HNPP 37.9 15.7 23.2 16.9 0 0 52.2 21.5 0.26 1.1 54 20.9 IgM PPN 64.3 14.2 11.7 12.6 20 30.4 65 40.9 0 0 52.7 9.3 CIDP 49 29.1 18.3 2.9 11.7 12.6 78.3 7.6 1.7 2.9 13.3 10.4 CMT1 28.4 24.4 8.8 17.5 16.3 32.5 67.5 39.5 0 0 18.8 8.5 CMT4B 4.19 1.6 0 0 0 0 100 0 0 0 100 0 Classification (Dyck et al15): A=normal; B=myelin wrinkling; C=demyelination; D=demyelination and remyelination; E=axonal degeneration; F=remyelination. HNPP=hereditary neuropathy with liability to pressure palsies; IgM PPN=IgM paraproteinemic neuropathy; CIDP=chronic inflammatory demyelinating polyneuropathy; CMT1=Charcot-Marie-Tooth disease type 1. CMT4B = Charcot-Marie-Tooth disease type 4B (HMSN with myelin outfolding). Table 2 Diameter and length of tomacula most frequent mechanism of tomacula forma- tion. Adaxonal myelin breakdown products (fig Age (y) Diameter (µm) Length (µm) 1 B) were most often seen in HNPP.
Load more

Recommended publications
  • Myelin Biogenesis Is Associated with Pathological Ultrastructure That Is
    bioRxiv preprint doi: https://doi.org/10.1101/2021.02.02.429485; this version posted February 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Myelin biogenesis is associated with pathological ultrastructure that 2 is resolved by microglia during development 3 4 5 Minou Djannatian1,2*, Ulrich Weikert3, Shima Safaiyan1,2, Christoph Wrede4, Cassandra 6 Deichsel1,2, Georg Kislinger1,2, Torben Ruhwedel3, Douglas S. Campbell5, Tjakko van Ham6, 7 Bettina Schmid2, Jan Hegermann4, Wiebke Möbius3, Martina Schifferer2,7, Mikael Simons1,2,7* 8 9 1Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany 10 2German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany 11 3Max-Planck Institute of Experimental Medicine, 37075 Göttingen, Germany 12 4Institute of Functional and Applied Anatomy, Research Core Unit Electron Microscopy, 13 Hannover Medical School, 30625, Hannover, Germany 14 5Department of Neuronal Remodeling, Graduate School of Pharmaceutical Sciences, Kyoto 15 University, Sakyo-ku, Kyoto 606-8501, Japan. 16 6Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3015 CN, 17 the Netherlands 18 7Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany 19 20 *Correspondence: [email protected] or [email protected] 21 Keywords 22 Myelination, degeneration, phagocytosis, microglia, oligodendrocytes, phosphatidylserine 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.02.02.429485; this version posted February 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • The Importance of Myelin
    The importance of myelin Nerve cell Nerves carry messages between different parts of the body insulating outer coating of nerves (myelin sheath) Normal nerve Damaged nerve myelin myelin sheath is sheath is intact damaged or destroyed message moves quickly message moves slowly Nerve cells transmit impulses Nerve cells have a long, thin, flexible fibre that transmits impulses. These impulses are electrical signals that travel along the length of the nerve. Nerve fibres are long to enable impulses to travel between distant parts of the body, such as the spinal cord and leg muscles. Myelin speeds up impulses Most nerve fibres are surrounded by an insulating, fatty sheath called myelin, which acts to speed up impulses. The myelin sheath contains periodic breaks called nodes of Ranvier. By jumping from node to node, the impulse can travel much more quickly than if it had to travel along the entire length of the nerve fibre. Myelinated nerves can transmit a signal at speeds as high as 100 metres per second – as fast as a Formula One racing car. normal damaged nerve nerve Loss of myelin leads to a variety of symptoms If the myelin sheath surrounding nerve fibres is damaged or destroyed, transmission of nerve impulses is slowed or blocked. The impulse now has to flow continuously along the whole nerve fibre – a process that is much slower than jumping from node to node. Loss of myelin can also lead to ‘short-circuiting’ of nerve impulses. An area where myelin has been destroyed is called a lesion or plaque. This slowing and ‘short-circuiting’ of nerve impulses by lesions leads to a variety of symptoms related to nervous system activity.
    [Show full text]
  • Regulation of Myelin Structure and Conduction Velocity by Perinodal Astrocytes
    Correction NEUROSCIENCE Correction for “Regulation of myelin structure and conduc- tion velocity by perinodal astrocytes,” by Dipankar J. Dutta, Dong Ho Woo, Philip R. Lee, Sinisa Pajevic, Olena Bukalo, William C. Huffman, Hiroaki Wake, Peter J. Basser, Shahriar SheikhBahaei, Vanja Lazarevic, Jeffrey C. Smith, and R. Douglas Fields, which was first published October 29, 2018; 10.1073/ pnas.1811013115 (Proc. Natl. Acad. Sci. U.S.A. 115,11832–11837). The authors note that the following statement should be added to the Acknowledgments: “We acknowledge Dr. Hae Ung Lee for preliminary experiments that informed the ultimate experimental approach.” Published under the PNAS license. Published online June 10, 2019. www.pnas.org/cgi/doi/10.1073/pnas.1908361116 12574 | PNAS | June 18, 2019 | vol. 116 | no. 25 www.pnas.org Downloaded by guest on October 2, 2021 Regulation of myelin structure and conduction velocity by perinodal astrocytes Dipankar J. Duttaa,b, Dong Ho Wooa, Philip R. Leea, Sinisa Pajevicc, Olena Bukaloa, William C. Huffmana, Hiroaki Wakea, Peter J. Basserd, Shahriar SheikhBahaeie, Vanja Lazarevicf, Jeffrey C. Smithe, and R. Douglas Fieldsa,1 aSection on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; bThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817; cMathematical and Statistical Computing Laboratory, Office of Intramural Research, Center for Information
    [Show full text]
  • The Myelin-Forming Cells of the Nervous System (Oligodendrocytes and Schwann Cells)
    The Myelin-Forming Cells of the Nervous System (oligodendrocytes and Schwann cells) Oligodendrocyte Schwann Cell Oligodendrocyte function Saltatory (jumping) nerve conduction Oligodendroglia PMD PMD Saltatory (jumping) nerve conduction Investigating the Myelinogenic Potential of Individual Oligodendrocytes In Vivo Sparse Labeling of Oligodendrocytes CNPase-GFP Variegated expression under the MBP-enhancer Cerebral Cortex Corpus Callosum Cerebral Cortex Corpus Callosum Cerebral Cortex Caudate Putamen Corpus Callosum Cerebral Cortex Caudate Putamen Corpus Callosum Corpus Callosum Cerebral Cortex Caudate Putamen Corpus Callosum Ant Commissure Corpus Callosum Cerebral Cortex Caudate Putamen Piriform Cortex Corpus Callosum Ant Commissure Characterization of Oligodendrocyte Morphology Cerebral Cortex Corpus Callosum Caudate Putamen Cerebellum Brain Stem Spinal Cord Oligodendrocytes in disease: Cerebral Palsy ! CP major cause of chronic neurological morbidity and mortality in children ! CP incidence now about 3/1000 live births compared to 1/1000 in 1980 when we started intervening for ELBW ! Of all ELBW {gestation 6 mo, Wt. 0.5kg} , 10-15% develop CP ! Prematurely born children prone to white matter injury {WMI}, principle reason for the increase in incidence of CP ! ! 12 Cerebral Palsy Spectrum of white matter injury ! ! Macro Cystic Micro Cystic Gliotic Khwaja and Volpe 2009 13 Rationale for Repair/Remyelination in Multiple Sclerosis Oligodendrocyte specification oligodendrocytes specified from the pMN after MNs - a ventral source of oligodendrocytes
    [Show full text]
  • Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Disease
    MOG ANTIBODY DISEASE Myelin Oligodendrocyte Glycoprotein (MOG) Antibody-Associated Encephalomyelitis WHAT IS MOG ANTIBODY-ASSOCIATED DEMYELINATION? Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination is an immune-mediated inflammatory process that affects the central nervous system (brain and spinal cord). MOG is a protein that exists on the outer surface of cells that create myelin (an insulating layer around nerve fibers). In a small number of patients, an initial episode of inflammation due to MOG antibodies may be the first manifestation of multiple sclerosis (MS). Most patients may only experience one episode of inflammation, but repeated episodes of central nervous system demyelination can occur in some cases. WHAT ARE THE SYMPTOMS? • Optic neuritis (inflammation of the optic nerve(s)) may be a symptom of MOG antibody- associated demyelination, which may result in painful loss of vision in one or both eyes. • Transverse myelitis (inflammation of the spinal cord) may cause a variety of symptoms that include: o Abnormal sensations. Numbness, tingling, coldness or burning in the arms and/or legs. Some are especially sensitive to the light touch of clothing or to extreme heat or cold. You may feel as if something is tightly wrapping the skin of your chest, abdomen or legs. o Weakness in your arms or legs. Some people notice that they're stumbling or dragging one foot, or heaviness in the legs. Others may develop severe weakness or even total paralysis. o Bladder and bowel problems. This may include needing to urinate more frequently, urinary incontinence, difficulty urinating and constipation. • Acute disseminated encephalomyelitis (ADEM) may cause loss of vision, weakness, numbness, and loss of balance, and altered mental status.
    [Show full text]
  • Targeting Myelin Lipid Metabolism As a Potential Therapeutic Strategy in a Model of CMT1A Neuropathy
    ARTICLE DOI: 10.1038/s41467-018-05420-0 OPEN Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy R. Fledrich 1,2,3, T. Abdelaal 1,4,5, L. Rasch1,4, V. Bansal6, V. Schütza1,3, B. Brügger7, C. Lüchtenborg7, T. Prukop1,4,8, J. Stenzel1,4, R.U. Rahman6, D. Hermes 1,4, D. Ewers 1,4, W. Möbius 1,9, T. Ruhwedel1, I. Katona 10, J. Weis10, D. Klein11, R. Martini11, W. Brück12, W.C. Müller3, S. Bonn 6,13, I. Bechmann2, K.A. Nave1, R.M. Stassart 1,3,12 & M.W. Sereda1,4 1234567890():,; In patients with Charcot–Marie–Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demye- lination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies. 1 Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen 37075, Germany.
    [Show full text]
  • The Effects of Normal Aging on Myelin and Nerve Fibers: a Review∗
    Journal of Neurocytology 31, 581–593 (2002) The effects of normal aging on myelin and nerve fibers: A review∗ ALAN PETERS Department of Anatomy and Neurobiology, Boston University School of Medicine, 715, Albany Street, Boston, MA 02118, USA [email protected] Received 7 January 2003; revised 4 March 2003; accepted 5 March 2003 Abstract It was believed that the cause of the cognitive decline exhibited by human and non-human primates during normal aging was a loss of cortical neurons. It is now known that significant numbers of cortical neurons are not lost and other bases for the cognitive decline have been sought. One contributing factor may be changes in nerve fibers. With age some myelin sheaths exhibit degenerative changes, such as the formation of splits containing electron dense cytoplasm, and the formation on myelin balloons. It is suggested that such degenerative changes lead to cognitive decline because they cause changes in conduction velocity, resulting in a disruption of the normal timing in neuronal circuits. Yet as degeneration occurs, other changes, such as the formation of redundant myelin and increasing thickness suggest of sheaths, suggest some myelin formation is continuing during aging. Another indication of this is that oligodendrocytes increase in number with age. In addition to the myelin changes, stereological studies have shown a loss of nerve fibers from the white matter of the cerebral hemispheres of humans, while other studies have shown a loss of nerve fibers from the optic nerves and anterior commissure in monkeys. It is likely that such nerve fiber loss also contributes to cognitive decline, because of the consequent decrease in connections between neurons.
    [Show full text]
  • Schwann Cells, but Not Oligodendrocytes, Depend Strictly
    RESEARCH ARTICLE Schwann cells, but not Oligodendrocytes, Depend Strictly on Dynamin 2 Function Daniel Gerber1†, Monica Ghidinelli1†, Elisa Tinelli1, Christian Somandin1, Joanne Gerber1, Jorge A Pereira1, Andrea Ommer1, Gianluca Figlia1, Michaela Miehe1, Lukas G Na¨ geli1, Vanessa Suter1, Valentina Tadini1, Pa´ ris NM Sidiropoulos1, Carsten Wessig2, Klaus V Toyka2, Ueli Suter1* 1Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland; 2Department of Neurology, University Hospital of Wu¨ rzburg, University of Wu¨ rzburg, Wu¨ rzburg, Germany Abstract Myelination requires extensive plasma membrane rearrangements, implying that molecules controlling membrane dynamics play prominent roles. The large GTPase dynamin 2 (DNM2) is a well-known regulator of membrane remodeling, membrane fission, and vesicular trafficking. Here, we genetically ablated Dnm2 in Schwann cells (SCs) and in oligodendrocytes of mice. Dnm2 deletion in developing SCs resulted in severely impaired axonal sorting and myelination onset. Induced Dnm2 deletion in adult SCs caused a rapidly-developing peripheral neuropathy with abundant demyelination. In both experimental settings, mutant SCs underwent prominent cell death, at least partially due to cytokinesis failure. Strikingly, when Dnm2 was deleted in adult SCs, non-recombined SCs still expressing DNM2 were able to remyelinate fast and efficiently, accompanied by neuropathy remission. These findings reveal a remarkable self-healing capability of peripheral nerves that are affected by SC loss. In the central nervous system, however, *For correspondence: we found no major defects upon Dnm2 deletion in oligodendrocytes. [email protected] DOI: https://doi.org/10.7554/eLife.42404.001 †These authors contributed equally to this work Competing interests: The Introduction authors declare that no Motor, sensory, and cognitive functions of the nervous system require rapid and refined impulse competing interests exist.
    [Show full text]
  • Normal Myelination a Practical Pictorial Review
    Normal Myelination A Practical Pictorial Review Helen M. Branson, BSc, MBBS, FRACR KEYWORDS Myelin Myelination T1 T2 MR Diffusion KEY POINTS MR imaging is the best noninvasive modality to assess myelin maturation in the human brain. A combination of conventional T1-weighted and T2-weighted sequences is all that is required for basic assessment of myelination in the central nervous system (CNS). It is vital to have an understanding of the normal progression of myelination on MR imaging to enable the diagnosis of childhood diseases including leukodystrophies as well as hypomyelinating disorders, delayed myelination, and acquired demyelinating disease. INTRODUCTION and its role in the human nervous system is needed. Assessment of the progression of myelin and mye- Myelin is present in both the CNS and the lination has been revolutionized in the era of MR peripheral nervous system. In the CNS, it is imaging. Earlier imaging modalities such as ultra- primarily found in white matter (although small sonography and computed tomography have no amounts are also found in gray matter) and thus current role or ability to contribute to the as- is responsible for its color.1 Myelin acts as an elec- sessment of myelin maturation or abnormalities trical insulator for neurons.1 Myelin plays a role in of myelin. The degree of brain myelination can be increasing the speed of an action potential by used as a marker of maturation. 10–100 times that of an unmyelinated axon1 and The authors discuss also helps in speedy axonal transport.2 Edgar 3 1. Myelin function and structure and Garbern (2004) demonstrated that the ab- 2.
    [Show full text]
  • Autophagy in Myelinating Glia
    256 • The Journal of Neuroscience, January 8, 2020 • 40(2):256–266 Viewpoints Autophagy in Myelinating Glia Jillian Belgrad,1 XRaffaella De Pace,2 and R. Douglas Fields1 1Section on Nervous System Development and Plasticity and 2Section on Intracellular Protein Trafficking, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 Autophagy is the cellular process involved in transportation and degradation of membrane, proteins, pathogens, and organelles. This fundamental cellular process is vital in development, plasticity, and response to disease and injury. Compared with neurons, little informationisavailableonautophagyinglia,butitisparamountforgliatoperformtheircriticalresponsestonervoussystemdiseaseand injury, including active tissue remodeling and phagocytosis. In myelinating glia, autophagy has expanded roles, particularly in phago- cytosis of mature myelin and in generating the vast amounts of membrane proteins and lipids that must be transported to form new myelin. Notably, autophagy plays important roles in removing excess cytoplasm to promote myelin compaction and development of oligodendrocytes, as well as in remyelination by Schwann cells after nerve trauma. This review summarizes the cell biology of autophagy, detailing the major pathways and proteins involved, as well as the roles of autophagy in Schwann cells and oligodendrocytes in develop- ment, plasticity, and diseases in which myelin is affected. This includes traumatic brain injury, Alexander’s
    [Show full text]
  • Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Current Insights Into the Disease Pathophysiology, Diagnosis and Management
    International Journal of Molecular Sciences Review Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Current Insights into the Disease Pathophysiology, Diagnosis and Management Wojciech Ambrosius 1,*, Sławomir Michalak 2, Wojciech Kozubski 1 and Alicja Kalinowska 2 1 Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Poznan, Poland; [email protected] 2 Department of Neurology, Division of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Poznan, Poland; [email protected] (S.M.); [email protected] (A.K.) * Correspondence: [email protected]; Tel.: +48-61-869-1535 Abstract: Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a rare, antibody-mediated inflammatory demyelinating disorder of the central nervous system (CNS) with various phenotypes starting from optic neuritis, via transverse myelitis to acute demyelinating encephalomyelitis (ADEM) and cortical encephalitis. Even though sometimes the clinical picture of this condition is similar to the presentation of neuromyelitis optica spectrum disorder (NMOSD), most experts consider MOGAD as a distinct entity with different immune system pathology. MOG is a molecule detected on the outer membrane of myelin sheaths and expressed primarily within the brain, spinal cord and also the optic nerves. Its function is not fully understood but this glycoprotein may act as a cell surface receptor or cell adhesion molecule. The specific outmost location of myelin makes it a potential target for autoimmune antibodies and cell-mediated responses in demyelinating processes. Optic neuritis seems to be the most frequent presenting phenotype in adults and ADEM in children. In adults, the disease course is multiphasic and subsequent relapses increase disability.
    [Show full text]
  • Mechanisms of Node of Ranvier Assembly
    REVIEWS Mechanisms of node of Ranvier assembly Matthew N. Rasband 1 ✉ and Elior Peles 2 ✉ Abstract | The nodes of Ranvier have clustered Na+ and K+ channels necessary for rapid and efficient axonal action potential conduction. However, detailed mechanisms of channel clustering have only recently been identified: they include two independent axon–glia interactions that converge on distinct axonal cytoskeletons. Here, we discuss how glial cell adhesion molecules and the extracellular matrix molecules that bind them assemble combinations of ankyrins, spectrins and other cytoskeletal scaffolding proteins, which cluster ion channels. We present a detailed molecular model, incorporating these overlapping mechanisms, to explain how the nodes of Ranvier are assembled in both the peripheral and central nervous systems. Axolemma In the early 1800s, engineers dreamed of communication mechanisms for their assembly have been revealed. In The plasma membrane of between North America and Europe using a transatlan- this Review, we emphasize and discuss nodal proteins the axon. tic telegraph cable. Their vision was realized in 1858 in the context of the multiple overlapping axon–glia and introduced a new ‘Age of Information'1. Although interactions that combine and converge on the axonal Extracellular matrix (ECM). A complex mixture of this earliest cable only transmitted a few words per cytoskeleton to efficiently cluster and maintain high + + extracellular macromolecules, hour, it still reduced the time required for the transmis- densities of Na and K channels at the nodes of Ranvier. including glycoproteins, that sion of a message by more than tenfold. Today, mod- surround cells. ern fibre- optic cable systems have further reduced this Myelinating glia control node assembly time to just milliseconds! However, these technological Myelination is a late developmental process mediated wonders lag ~400 million years behind the revolution by Schwann cells in the peripheral nervous system in speed of axonal action potential conduction that (PNS) and oligodendrocytes in the CNS.
    [Show full text]