Myelin biology and repair articles within Nature Communications

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• Article
  11 March 2024 | Open Access

  Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination

  Factors limiting CNS remyelination with age are poorly understood. Here the authors show that aged Treg lose capacity to support CNS remyelination in mice, which can be restored in a young environment.

  • Alerie Guzman de la Fuente
  • , Marie Dittmer
  •  & Denise C. Fitzgerald

• Article
  27 February 2024 | Open Access

  Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons

  Myelinated axons vary in diameter by over 100-fold. Here, the authors identify a role for the nuclear transport receptor importin 13 in axon diameter growth and corresponding increases to conduction speed along myelinated axons.

  • Jenea M. Bin
  • , Daumante Suminaite
  •  & David A. Lyons

• Article
  04 January 2024 | Open Access

  Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension

  The cell biological mechanisms that govern myelin sheath extension remain incompletely understood. Here, the authors find that calcium signaling in oligodendrocytes is required for the actin-dependent extension of myelin sheaths.

  • Manasi Iyer
  • , Husniye Kantarci
  •  & J. Bradley Zuchero

• Article
  21 December 2023 | Open Access

  ANKS1B encoded AIDA-1 regulates social behaviors by controlling oligodendrocyte function

  Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome. Here the authors show this syndrome is associated with impaired white matter integrity, and that Anks1b-deficient mouse models display deficits in oligodendrocyte maturation, myelination, and Rac1 function.

  • Chang Hoon Cho
  • , Ilana Vasilisa Deyneko
  •  & Bryen A. Jordan

• Article
  04 November 2023 | Open Access

  Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination in male mice

  Myelination is often compromised in ATR-X intellectual disability syndrome patients. Here, the authors show that the causative gene, ATRX, can regulate myelination in mice by modulating systemic thyroxine levels and by supporting oligodendrocyte progenitor differentiation.

  • Megan E. Rowland
  • , Yan Jiang
  •  & Nathalie G. Bérubé

• Article
  30 October 2023 | Open Access

  Microglia-mediated demyelination protects against CD8⁺ T cell-driven axon degeneration in mice carrying PLP defects

  Demyelination is often suggested to cause axonal degeneration. Here, the authors study mice carrying distinct PLP defects and reveal how persistent ensheathment with perturbed myelin poses a risk for CD8 + T cell-driven axon loss and behavioral decline.

  • Janos Groh
  • , Tassnim Abdelwahab
  •  & Rudolf Martini

• Article
  14 October 2023 | Open Access

  Oligodendrocyte dynamics dictate cognitive performance outcomes of working memory training in mice

  How and to what extent oligodendrocytes (OLs) contribute to learning and cognition is not well understood. Here, the authors show that the performance of mice in working memory-dependent cognitive tasks depends on OL genesis and is proportional to the number of OL precursors and OLs generated during training.

  • Takahiro Shimizu
  • , Stuart G. Nayar
  •  & William D. Richardson

• Article
  08 June 2023 | Open Access

  Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration

  The mechanisms regulating central nervous system remyelination efficiency are poorly understood. Here, the authors show that remyelination is driven by astrocytes supporting oligodendrocyte survival, regulated by the Nrf2 and cholesterol pathways.

  • Irene Molina-Gonzalez
  • , Rebecca K. Holloway
  •  & Veronique E. Miron

• Article
  09 December 2022 | Open Access

  Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes

  How myelin controls energy usage in different neuronal cell types remains unclear. Here, using viral tools, live imaging and ultrastructural data, the authors show that in contrast to excitatory axons interneuron myelination boosts the clustering of mitochondria.

  • Koen Kole
  • , Bas J. B. Voesenek
  •  & Maarten H. P. Kole

• Article
  10 November 2022 | Open Access

  Vascular endothelium deploys caveolin-1 to regulate oligodendrogenesis after chronic cerebral ischemia in mice

  OPC-vascular coupling contributes to myelin maintenance. Here the authors show Cav-1 stabilizes interactions and mediates OPC maturation in ischemia.

  • Ying Zhao
  • , Wusheng Zhu
  •  & Xinfeng Liu

• Article
  05 November 2022 | Open Access

  Diffusion MRI anisotropy in the cerebral cortex is determined by unmyelinated tissue features

  In gray matter, the relative contributions of myelinated axons and other tissue features to diffusion MRI (dMRI) are poorly understood. Here the authors combine ex vivo high-resolution dMRI of marmoset brain with histological sections of the same brain, and their findings suggest that in cortex, dMRI does not match the spatial distribution of myelin in the gray matter.

  • Colin Reveley
  • , Frank Q. Ye
  •  & David A. Leopold

• Article
  23 September 2022 | Open Access

  CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes

  Understanding myelination is important for CNS plasticity and disease. Here the authors show exocytosis mediated by the vesicular SNARE proteins VAMP2/3 is involved in oligodendrocyte membrane expansion.

  • Mable Lam
  • , Koji Takeo
  •  & J. Bradley Zuchero

• Article
  06 September 2022 | Open Access

  Ultrafast and hypersensitive phase imaging of propagating internodal current flows in myelinated axons and electromagnetic pulses in dielectrics

  The authors introduce differentially enhanced compressed ultrafast photography, a phase imaging platform that combines high speed and sensitivity. They visualise propagation of passive current flows along myelinated axons, and electromagnetic pulses in lithium niobate.

  • Yide Zhang
  • , Binglin Shen
  •  & Lihong V. Wang

• Article
  22 July 2022 | Open Access

  A macroscopic link between interhemispheric tract myelination and cortico-cortical interactions during action reprogramming

  Myelination is a key regulator of brain function. Here the authors use MR-based myelin measures to examine if cortico-cortical interactions, as assessed by paired pulse transcranial magnetic stimulation, are affected by variations in myelin in the human brain.

  • Alberto Lazari
  • , Piergiorgio Salvan
  •  & Heidi Johansen-Berg

• Article
  28 April 2022 | Open Access

  Molecular and functional heterogeneity in dorsal and ventral oligodendrocyte progenitor cells of the mouse forebrain in response to DNA damage

  Here the authors show that, depending on their distinct developmental origins and ability to counteract oxidative stress, dorsal and ventral oligodendrocyte progenitor cells of the postnatal mouse brain are differentially vulnerable to DNA damage.

  • Enrica Boda
  • , Martina Lorenzati
  •  & Annalisa Buffo

• Article
  17 March 2022 | Open Access

  The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents

  Transcription factors regulate gene programs during myelination. Here, the authors show that the Oligodendrocyte Transcription Factor 2 (OLIG2) regulates the differentiation of oligodendrocyte progenitor cells into immature oligodendrocytes via SETDB1 during myelination and remyelination in rodents.

  • Kunkun Zhang
  • , Shaoxuan Chen
  •  & Wei Mo

• Article
  04 March 2022 | Open Access

  White matter integrity in mice requires continuous myelin synthesis at the inner tongue

  Myelin is formed of proteins of long half-lives. The mechanisms of renewal of such a stable structure are unclear. Here, the authors show that myelin integrity requires continuous myelin synthesis at the inner tongue, contributing to the maintenance of a functional axon-myelin unit.

  • Martin Meschkat
  • , Anna M. Steyer
  •  & Wiebke Möbius

• Article
  01 September 2021 | Open Access

  Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination

  Microglia are important for brain homeostasis and plasticity. The mechanisms underlying microglia-neuron interactions are still unclear. Here, the authors show that microglia preferentially interact with the nodes of Ranvier along axons. This interaction is modulated by neuronal activity and contributes to remyelination in mice.

  • R. Ronzano
  • , T. Roux
  •  & A. Desmazières

• Article
  26 August 2021 | Open Access

  Oligodendrocytic Na⁺-K⁺-Cl^– co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain

  Brain plasticity declines with age. Here, the authors show that NKCC1 regulates oligodendrocyte activity, facilitating neuronal plasticity during juvenile. Inducing activation of oligodendrocytic NKCC1 results in restoration of neuronal plasticity in the adult mouse brain.

  • Yoshihiko Yamazaki
  • , Yoshifumi Abe
  •  & Kenji F. Tanaka

• Article
  24 August 2021 | Open Access

  Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain

  Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelination during development and remyelination in mice.

  • Ming Zhang
  • , Jian Wang
  •  & Xianghui Zhao

• Article
  06 August 2021 | Open Access

  Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

  Myelination patterns of different neurons in grey matter have not been fully defined. Here, the authors show that axon diameter and neuronal identity influence myelination patterns in the intact mouse somatosensory cortex. In vivo imaging revealed that remyelination altered myelin patterns but restored overall myelin content on distinct neuron subtypes.

  • Cody L. Call
  •  & Dwight E. Bergles

• Article
  07 June 2021 | Open Access

  TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice

  Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelin repair in adult mice, but is defective with aging.

  • Sarah Moyon
  • , Rebecca Frawley
  •  & Patrizia Casaccia

• Article
  02 June 2021 | Open Access

  Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells

  Prohibitin 2 can localize to the axon-Schwann-cell interface and is required for myelin formation. Here, the authors show that deletion of prohibitin 1 in Schwann cells instead triggers severe myelin loss likely caused by mitochondrial dysfunction, and not rescued by inhibition of the ensuing integrated stress response.

  • Gustavo Della-Flora Nunes
  • , Emma R. Wilson
  •  & M. Laura Feltri

• Article
  19 May 2021 | Open Access

  Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue

  Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.

  • Marios Georgiadis
  • , Aileen Schroeter
  •  & Markus Rudin

• Article
  21 April 2021 | Open Access

  AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A

  Charcot-Marie-Tooth disease 1 A (CMT1A) results from PMP22 gene duplication and is characterized by peripheral nerve myelination deficits. Here, the authors prevent the development of pathological features in a rat model of CMT1A through the local delivery of AAV2/9 expressing shRNAs against PMP22.

  • Benoit Gautier
  • , Helene Hajjar
  •  & Nicolas Tricaud

• Article
  15 April 2021 | Open Access

  Microglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor

  Oligodendrocyte precursor cell (OPC) proliferation and differentiation is greater in white matter than gray matter. Here, the authors show regulation of OPC proliferation in white matter involved trans-activation of PDGFRα on OPCs via Nrp1 expressed by adjacent microglia.

  • Amin Sherafat
  • , Friederike Pfeiffer
  •  & Akiko Nishiyama

• Article
  13 October 2020 | Open Access

  Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits

  Myelination optimizes conduction speed of excitatory neurons. However, whether myelination of interneurons (INs) refines cortical networks is unclear. Here, the authors show that INs myelination shapes feedforward inhibition of mouse cortical sensory circuits and impacts whisker-mediated behaviour.

  • Najate Benamer
  • , Marie Vidal
  •  & María Cecilia Angulo

• Article
  29 September 2020 | Open Access

  Myelin replacement triggered by single-cell demyelination in mouse cortex

  Myelination is a highly regulated phenomenon. Here, the authors show that demyelination induced by the loss of a single oligodendrocyte triggers replenishment of a specific fraction the original myelin and myelination of previously unmyelinated axons in the mouse cortex.

  • Nicolas Snaidero
  • , Martina Schifferer
  •  & Thomas Misgeld

• Article
  13 August 2020 | Open Access

  Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis

  Impaired oligodendrocyte (OL) differentiation and remyelination after myelin damage in multiple sclerosis is associated with neurodegeneration. The authors show that Gsta4 is expressed during adult OL differentiation and identify it as a regulator of OL differentiation, survival, and remyelination.

  • Karl E. Carlström
  • , Keying Zhu
  •  & Fredrik Piehl

• Article
  09 July 2020 | Open Access

  EEF1A1 deacetylation enables transcriptional activation of remyelination

  The molecular mechanisms regulating remyelination are unclear. Here, the authors show that promoting deacetylation of eEF1A1 prevents the translocation of Sox10 outside the nucleus, contributing to maintaining the expression of Sox10 target genes and increasing remyelination efficiency.

  • Mert Duman
  • , Adrien Vaquié
  •  & Claire Jacob

• Article
  05 June 2020 | Open Access

  Rab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth

  Charcot-Marie-Tooth (CMT) is an inherited peripheral neuropathy. Here, the authors show that Rab35 forms a complex with genes implicated in CMT, MTMR13 and MTMR2, which regulates myelin growth by controlling mTORC1 signaling through lipid turnover.

  • Linda Sawade
  • , Federica Grandi
  •  & Volker Haucke

• Article
  01 May 2020 | Open Access

  Lipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury

  The regeneration dynamics following peripheral nerve injury differs among species. Here, the authors compared transcriptomic and lipid metabolism changes in murine and human Schwann cells in vivo and ex vivo sural nerves, underlying their switch from myelinating to repair state following injury.

  • Sofia Meyer zu Reckendorf
  • , Christine Brand
  •  & Bernd Knöll

• Article
  19 February 2020 | Open Access

  Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery

  Hypoxic brain damage associated with premature birth causes lasting neurological impairments. Here, the authors use environmental enrichment to rescue white matter dysmaturation following hypoxia, while identifying a critical window of intervention and oligodendrocyte-specific changes in gene expression.

  • Thomas A. Forbes
  • , Evan Z. Goldstein
  •  & Vittorio Gallo

• Article
  11 September 2019 | Open Access

  Oligodendrocytes express synaptic proteins that modulate myelin sheath formation

  Oligodendrocyte processes can detect and respond to axonal vesicular release. The authors here show in zebrafish that transsynaptic adhesion molecules, molecules that promote synapse formation and maturation in neurons, are expressed by oligodendrocytes and required for myelin sheath growth.

  • Alexandria N. Hughes
  •  & Bruce Appel

• Article
  29 August 2019 | Open Access

  Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination

  In multiple sclerosis (MS), antigen-presenting cells inducing cytotoxic T cell response against mature oligodendrocytes remain to be identified. Here the authors show that oligodendrocyte precursors cross-present antigen taken up from mature oligodendrocytes, and are targeted by cytotoxic T cells in cell culture and in an animal model of MS.

  • Leslie Kirby
  • , Jing Jin
  •  & Peter A. Calabresi

• Article
  05 July 2019 | Open Access

  Myelinating Schwann cells ensheath multiple axons in the absence of E3 ligase component Fbxw7

  The authors find that deletion from Schwann cells of an E3 ubiquitin ligase component called Fbxw7 leads to a phenotype reminiscent of myelination in the central nervous system where a single oligodendrocyte ensheaths multiple axons.

  • Breanne L. Harty
  • , Fernanda Coelho
  •  & Kelly R. Monk

• Article
  15 January 2019 | Open Access

  Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation

  Chitinase 3-like-3 (Chi3l3) is expressed in microglia, but its function is not clear. Here the authors show that Chi3l3 is expressed in the subventricular zone in mouse experimental immune encephalitis, which induces oligodendrogenesis.

  • Sarah C. Starossom
  • , Juliana Campo Garcia
  •  & Samia J. Khoury

• Article
  03 August 2018 | Open Access

  Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination

  The contribution of oligodendrocytes to remyelination in functional recovery after spinal cord injury is not fully understood. Here, the authors show that oligodendrocyte progenitor cell differentiation is not required for functional recovery after spinal cord injury in mice.

  • Greg J. Duncan
  • , Sohrab B. Manesh
  •  & Wolfram Tetzlaff

• Article
  02 August 2018 | Open Access

  Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy

  Charcot–Marie–Tooth disease 1A (CMT1A) is a peripheral demyelinating disease. Here, the authors demonstrate in a rodent model of CMT1A that Schwann cells have impairments in lipid biosynthesis, and that restoring lipids via diet can reverse the dysmyelinating phenotype in these animals.

  • R. Fledrich
  • , T. Abdelaal
  •  & M. W. Sereda

• Article
  12 March 2018 | Open Access

  Vesicular glutamate release from central axons contributes to myelin damage

  Neuronal activity can lead to vesicular release of glutamate. Here the authors demonstrate that vesicular release of glutamate occurs in axons during ischemic conditions, and that an allosteric modulator of GluN2C/D is protective in models of ischemic injury.

  • Sean Doyle
  • , Daniel Bloch Hansen
  •  & Robert Fern

• Article
  02 January 2018 | Open Access

  Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination

  Following demyelination injury, neural stem cells (NSCs) in the subventricular zone switch to an activated state. Here, the authors show that a transient shift from non-canonical to canonical Wnt signaling is necessary for activation of quiescent NSCs to achieve tissue homeostasis and brain repair.

  • Manideep Chavali
  • , Michael Klingener
  •  & Adan Aguirre

• Article
  28 November 2017 | Open Access

  Label-free nanoscale optical metrology on myelinated axons in vivo

  Spectral reflectance has been used to achieve label-free, in vivo imaging of myelin, a membranous sheath that allows faster electrical conduction along neuronal axons. Here the authors extend this technique to measure nanoscale features, including changes following traumatic brain injury.

  • Junhwan Kwon
  • , Moonseok Kim
  •  & Myunghwan Choi

• Article
  24 January 2017 | Open Access

  Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

  Cholesterol is important for axonal myelination during development. Here the authors show that cholesterol levels are reduced in a cuprizone mouse model of multiple sclerosis and that dietary cholesterol supplementation enhances remyelination and recovery.

  • Stefan A. Berghoff
  • , Nina Gerndt
  •  & Gesine Saher

• Article
  23 November 2016 | Open Access

  VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination

  The vascular cell adhesion molecule VCAM1 plays a role in the immune system but is also expressed in oligodendrocytes. Here, the authors find VCAM1 interacts with neuronal α4 integrin to regulate oligodendrocyte differentiation and thereby myelination, an effect mediated by downstream CD69 signalling.

  • Yuki Miyamoto
  • , Tomohiro Torii
  •  & Junji Yamauchi

• Article
  16 November 2016 | Open Access

  Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model

  Oligodendrocyte damage is a key component of demyelinating diseases. Here, the authors use in vivolight and correlated electron microscopy in EAE mouse models, and find early damage occurs at the myelin sheath before spreading to the oligodendrocyte cell body.

  • Elisa Romanelli
  • , Doron Merkler
  •  & Martin Kerschensteiner

• Article
  31 October 2016 | Open Access

  Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

  Sensitive and label-free imaging methods to visualize nerve degeneration are currently lacking. Here authors show that stimulated Raman scattering (SRS) microscopy can be used to monitor peripheral nerve degeneration in mouse models of amyotrophic lateral sclerosis (ALS) and in postmortem tissue from ALS patients.

  • Feng Tian
  • , Wenlong Yang
  •  & Kevin Eggan

• Article
  20 July 2016 | Open Access

  Optimal myelin elongation relies on YAP activation by axonal growth and inhibition by Crb3/Hippo pathway

  Molecular mechanisms regulating optimal myelin geometry are only partially understood. Here authors show that peripheral myelin growth is orchestrated by the Crb3/Hippo/YAP pathway, and that defects in YAP activation may underlie peripheral neuropathies caused by shorter myelin.

  • Ruani N. Fernando
  • , Laurent Cotter
  •  & Nicolas Tricaud

• Article
  26 April 2016 | Open Access

  An inhibitor of chondroitin sulfate proteoglycan synthesis promotes central nervous system remyelination

  Chondroitin sulfate proteoglycans (CSPGs) secreted by astrocytes are known to inhibit OPC differentiation and remyelination. Here, the authors identify a novel CSPG synthesis inhibitor and find it can rescue OPC differentiation in vitroand accelerate remyelination in mice following focal demyelination.

  • Michael B. Keough
  • , James A. Rogers
  •  & V. Wee Yong

• Article
  04 April 2016 | Open Access

  Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination

  Current treatments of multiple sclerosis are aimed at immunosuppression. Here the authors show that kappa opioid receptor is important for oligodendrocyte differentiation and myelination and the receptor agonists are protective in a mouse model of multiple sclerosis.

  • Changsheng Du
  • , Yanhui Duan
  •  & Xin Xie

• Article
  06 October 2015 | Open Access

  Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors

  Myelin regeneration can occur spontaneously in demyelinating diseases but the underlying mechanisms are incompletely understood. Here the authors show that neuronal activity and glutamatergic synapses instruct oligodendrocyte progenitor cells to differentiate into new myelinating oligodendrocytes.

  • Hélène O. B. Gautier
  • , Kimberley A. Evans
  •  & Ragnhildur T Káradóttir