New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination
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Abstract
Oligodendrocytes that survive demyelination can remyelinate, including in multiple sclerosis (MS), but how they do so is unclear. In this study, using zebrafish, we found that surviving oligodendrocytes make few new sheaths and frequently mistarget new myelin to neuronal cell bodies, a pathology we also found in MS. In contrast, oligodendrocytes generated after demyelination make abundant and correctly targeted sheaths, indicating that they likely also have a better regenerative potential in MS.
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Newly formed cells might be much more efficient compared to surviving oligodendrocytes.
“and it has been demonstrated that newly formed cells might be much more efficient compared to surviving oligodendrocytes.”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [27]
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Cites
An updated histological classification system for multiple sclerosis lesions
Kuhlmann, T., Ludwin, S., Prat, A., Antel, J., Brück, W., & Lassmann, H. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1653-y · Cited by 692 · see citing works
Regenerating CNS myelin — from mechanisms to experimental medicines
Franklin, R. J. M., & ffrench-Constant, C. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.136 · Cited by 647 · see citing works
Dynamics of Oligodendrocyte Generation and Myelination in the Human Brain
Yeung, M. S. Y., Zdunek, S., Bergmann, O., Bernard, S., Salehpour, M., Alkass, K., Perl, S., Tisdale, J., Possnert, G., Brundin, L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.011 · Cited by 541 · see citing works
Dynamics of oligodendrocyte generation in multiple sclerosis
Yeung, M. S. Y., Djelloul, M., Steiner, E., Bernard, S., Salehpour, M., Possnert, G., Brundin, L., & Frisén, J. (2019) · Nature · doi:10.1038/s41586-018-0842-3 · Cited by 376 · see citing works
Central nervous system regeneration is driven by microglia necroptosis and repopulation
Lloyd, A. F., Davies, C. L., Holloway, R. K., Labrak, Y., Ireland, G., Carradori, D., Dillenburg, A., Borger, E., Soong, D., Richardson, J. C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0418-z · Cited by 316 · see citing works
Self-citationIndividual axons regulate the myelinating potential of single oligodendrocytes in vivo
Almeida, R. G., Czopka, T., ffrench-Constant, C., & Lyons, D. A. (2011) · Development · doi:10.1242/dev.071001 · Cited by 214 · see citing works
Self-citationRemyelination alters the pattern of myelin in the cerebral cortex
Orthmann-Murphy, J., Call, C. L., Molina-Castro, G. C., Hsieh, Y. C., Rasband, M. N., Calabresi, P. A., & Bergles, D. E. (2020) · eLife · doi:10.7554/elife.56621 · Cited by 111 · see citing works
Flagged first, then by citations
Research works printed but not linked: 28
- [1]Thompson AJ Baranzini SE Geurts J Hemmer B Ciccarelli O Multiple sclerosis Lancet 2018 391 1622 1636 29576504
- [2]Franklin RJM Frisén J Lyons DA Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin Semin Cell Dev Biol 2020 116 3 9 33082115
- [3]Cole KLH Early JJ Lyons DA Drug discovery for remyelination and treatment of MS Glia 2017 65 1565 1589 28618073
- [5]Duncan ID The adult oligodendrocyte can participate in remyelination Proc Natl Acad Sci U S A 2018 115 E11807 E11816 30487224 PMC6294923
- [6]Bacmeister CM Motor learning promotes remyelination via new and surviving oligodendrocytes Nat Neurosci 2020 23 819 831 32424285 PMC7329620
- [7]Klingseisen A Oligodendrocyte Neurofascin Independently Regulates Both Myelin Targeting and Sheath Growth in the CNS Article Oligodendrocyte Neurofascin Independently Regulates Both Myelin Targeting and Sheath Growth in the CNS Dev Cell 2019 51 730 744 31761670 PMC6912162
- [8]Almeida RG Myelination of Neuronal Cell Bodies when Myelin Supply Exceeds Axonal Demand Curr Biol 2018 28 1296 1305 29628374 PMC5912901
- [9]Czopka T ffrench-Constant C Lyons DA Individual oligodendrocytes have only a few hours in which to generate new myelin sheaths invivo Dev Cell 2013 25 599 609 23806617 PMC4013507
- [10]Auer F Vagionitis S Czopka T Evidence for Myelin Sheath Remodeling in the CNS Revealed by In Vivo Imaging Curr Biol 2018 28 549 559 29429620
- [11]Harboe M Torvund-Jensen J Kjaer-Sorensen K Laursen LS Ephrin-A1-EphA4 signaling negatively regulates myelination in the central nervous system Glia 2018 66 934 950 29350423
- [12]Wolf RM Wilkes JJ Chao MV Resh MD Tyrosine Phosphorylation of p190 RhoGAP by Fyn Regulates Oligodendrocyte Differentiation J Neurobiol 2001 49 62 78 11536198
- [13]Albert M Antel J Brück W Stadelmann C Extensive Cortical Remyelination in Patients with Chronic Multiple Sclerosis Brain Pathol 2007 17 129 138 17388943 PMC8095564
- [14]Snaidero N Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue Cell 2014 156 277 290 24439382 PMC4862569
- [15]Hughes EG Orthmann-Murphy JL Langseth AJ Bergles DE Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex Nat Neurosci 2018 21 696 708 29556025 PMC5920726
- [16]Hill RA Patel KD Goncalves CM Grutzendler J Nishiyama A Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division Nat Neurosci 2014 17 1518 1529 25262495 PMC4275302
- [18]Jäkel S Altered human oligodendrocyte heterogeneity in multiple sclerosis Nature 2019 566 543 547 30747918 PMC6544546
- [19]Kirby BB In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development 2006 9 1506 1511 17099706
- [20]Hughes EG Kang SH Fukaya M Bergles DE Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain Nat Neurosci 2013 16 668 679 23624515 PMC3807738
- [22]Ellett F Pase L Hayman JW Andrianopoulos A Lieschke GJ Phagocytes, Granulocytes, and Myelopoiesis mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish Blood 2011 27 e49 e56 PMC3056479 21084707
- [23]Bin JM Lyons DA Imaging Myelination In Vivo Using Transparent Animal Models Brain Plast 2016 2 3 29 29765846 PMC5928531
- [24]Baraban M Koudelka S Lyons DA Ca 2+ activity signatures of myelin sheath formation and growth in vivo Nat Neurosci 2018 21 19 25 29230058 PMC5742537
- [25]Hamilton nicolaB Kolodziejczyk K Kougioumtzidou E Attwell D Proton-gated Ca 2+-permeable TRP channels damage myelin in conditions mimicking ischaemia Nature 2016 529 523 527 26760212 PMC4733665
- [26]Paez PM Lyons DA Annual Review of Neuroscience Calcium Signaling in the Oligodendrocyte Lineage: Regulators and Consequences Annu Rev Neurosci 2020 43 163 186 (2020) 32075518
- [27]Chen S Chiu CN McArthur KL Fetcho JR Prober DA TRP channel mediated neuronal activation and ablation in freely behaving zebrafish Nat Methods 2016 13 147 150 26657556 PMC4851460
- [28]Kwan KM The Tol2kit: A Multisite Gateway-Based Construction Kit for Tol2 Transposon Transgenesis Constructs Dev Dyn 2007 236 3088 3099 17937395
- [29]Karttunen MJ Regeneration of myelin sheaths of normal length and thickness in the zebrafish CNS correlates with growth of axons in caliber PLoS One 2017 12 1 27 PMC5444792 28542521
- [30]Early JJ An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination Elife 2018 7 1 31 PMC6056238 29979149
- [31]Nicaise AM Cellular senescence in progenitor cells contributes to diminished remyelination potential in progressive multiple sclerosis Proc Natl Acad Sci 2019 116 9030 9039 30910981 PMC6500153
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BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis
Bergner, C. G., van der Meer, F., Franz, J., Vakrakou, A., Würfel, T., Nessler, S., Schäfer, L., Nau-Gietz, C., Winkler, A., Lagumersindez-Denis, N., et al. (2025) · Brain · doi:10.1093/brain/awae293 · Cited by 16 · see citing works
Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination
Loo, H. K., Gallegos, J., Mialki, C., Perrin, G. E., Malloy, T., & Orthmann‐Murphy, J. L. (2026) · Glia · doi:10.1002/glia.70120 · Cited by 2 · see citing works
- Authors
- Neely, S. A., Williamson, J. M., Klingseisen, A., Zoupi, L., Early, J. J., Williams, A., & Lyons, D. A.
- Affiliations
- Multiple Sclerosis Society (GB)
- Corresponding author
- Lyons, David A.
- Venue
- Nature Neuroscience
- Published
- 2022-02-14
- Volume
- 25
- Issue
- 4
- Pages
- 415-420
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC7612594
- OpenAlex
- W4220944763
- Cited by
- 132
- References
- 7
- Citations by year
- 2026: 12 · 2025: 25 · 2024: 38 · 2023: 23 · 2022: 18 · 2021: 12 · 2020: 4
- FWCI
- 18.48
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (108906/Z/15/Z, 214244/Z/18/Z)
- Multiple Sclerosis Society (NA)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- oligodendrocytes, remyelination, demyelination, multiple sclerosis, myelin sheath regeneration, neuronal cell bodies, oligodendrocyte regeneration, zebrafish
- MeSH terms
- Animals, Demyelinating Diseases, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, Regeneration, Zebrafish
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