IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39046-8.html
   My bibliography  Save this article

Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration

Author

Listed:
  • Irene Molina-Gonzalez

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Rebecca K. Holloway

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Zoeb Jiwaji

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh)

  • Owen Dando

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh)

  • Sarah A. Kent

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh
    Wellcome Trust Translational Neuroscience PhD programme)

  • Katie Emelianova

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh)

  • Amy F. Lloyd

    (University of Dundee)

  • Lindsey H. Forbes

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Ayisha Mahmood

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Thomas Skripuletz

    (Medizinische Hochschule Hannover)

  • Viktoria Gudi

    (Medizinische Hochschule Hannover)

  • James A. Febery

    (University of Edinburgh)

  • Jeffrey A. Johnson

    (University of Wisconsin
    University of Wisconsin
    University of Wisconsin
    University of Wisconsin)

  • Jill H. Fowler

    (University of Edinburgh)

  • Tanja Kuhlmann

    (University Hospital Muenster)

  • Anna Williams

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh)

  • Siddharthan Chandran

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh)

  • Martin Stangel

    (Medizinische Hochschule Hannover)

  • Andrew J. M. Howden

    (University of Dundee)

  • Giles E. Hardingham

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh)

  • Veronique E. Miron

    (United Kingdom Dementia Research Institute at The University of Edinburgh, Edinburgh Medical School
    University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

Abstract

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned male mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.

Suggested Citation

  • Irene Molina-Gonzalez & Rebecca K. Holloway & Zoeb Jiwaji & Owen Dando & Sarah A. Kent & Katie Emelianova & Amy F. Lloyd & Lindsey H. Forbes & Ayisha Mahmood & Thomas Skripuletz & Viktoria Gudi & Jame, 2023. "Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39046-8
    DOI: 10.1038/s41467-023-39046-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39046-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39046-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Zita Hubler & Dharmaraja Allimuthu & Ilya Bederman & Matthew S. Elitt & Mayur Madhavan & Kevin C. Allan & H. Elizabeth Shick & Eric Garrison & Molly Karl & Daniel C. Factor & Zachary S. Nevin & Joel L, 2018. "Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination," Nature, Nature, vol. 560(7718), pages 372-376, August.
    2. Peter Huppke & Susann Weissbach & Joseph A. Church & Rhonda Schnur & Martina Krusen & Steffi Dreha-Kulaczewski & W. Nikolaus Kühn-Velten & Annika Wolf & Brenda Huppke & Francisca Millan & Amber Begtru, 2017. "Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    3. Zheng Wu & Matthew Parry & Xiao-Yi Hou & Min-Hui Liu & Hui Wang & Rachel Cain & Zi-Fei Pei & Yu-Chen Chen & Zi-Yuan Guo & Sambangi Abhijeet & Gong Chen, 2020. "Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington’s disease," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    4. Lucas Schirmer & Dmitry Velmeshev & Staffan Holmqvist & Max Kaufmann & Sebastian Werneburg & Diane Jung & Stephanie Vistnes & John H. Stockley & Adam Young & Maike Steindel & Brian Tung & Nitasha Goya, 2019. "Neuronal vulnerability and multilineage diversity in multiple sclerosis," Nature, Nature, vol. 573(7772), pages 75-82, September.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chen Chen & Yaqing Shu & Chengkai Yan & Huilu Li & Zhenchao Huang & ShiShi Shen & Chunxin Liu & Yanjun Jiang & Shixiong Huang & Zhanhang Wang & Feng Mei & Feng Qin & Xiaodong Liu & Wei Qiu, 2024. "Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Daniela Rodrigues-Amorim & P. Lorenzo Bozzelli & TaeHyun Kim & Liwang Liu & Oliver Gibson & Cheng-Yi Yang & Mitchell H. Murdock & Fabiola Galiana-Melendez & Brooke Schatz & Alexis Davison & Md Rezaul , 2024. "Multisensory gamma stimulation mitigates the effects of demyelination induced by cuprizone in male mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Jarne Beliën & Stijn Swinnen & Robbe D’hondt & Laia Verdú de Juan & Nina Dedoncker & Patrick Matthys & Jan Bauer & Celine Vens & Sinéad Moylett & Bénédicte Dubois, 2024. "CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Florian Pernin & Qiao-Ling Cui & Abdulshakour Mohammadnia & Milton G. F. Fernandes & Jeffery A. Hall & Myriam Srour & Roy W. R. Dudley & Stephanie E. J. Zandee & Wendy Klement & Alexandre Prat & Hanna, 2024. "Regulation of stress granule formation in human oligodendrocytes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Janos Groh & Tassnim Abdelwahab & Yogita Kattimani & Michaela Hörner & Silke Loserth & Viktoria Gudi & Robert Adalbert & Fabian Imdahl & Antoine-Emmanuel Saliba & Michael Coleman & Martin Stangel & Mi, 2023. "Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Majid Pahlevan Kakhki & Antonino Giordano & Chiara Starvaggi Cucuzza & Tejaswi Venkata S. Badam & Samudyata Samudyata & Marianne Victoria Lemée & Pernilla Stridh & Asimenia Gkogka & Klementy Shchetyns, 2024. "A genetic-epigenetic interplay at 1q21.1 locus underlies CHD1L-mediated vulnerability to primary progressive multiple sclerosis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Giorgia Maria Ferlazzo & Anna Maria Gambetta & Sonia Amato & Noemi Cannizzaro & Silvia Angiolillo & Mattia Arboit & Linda Diamante & Elena Carbognin & Patrizia Romani & Federico La Torre & Elena Galim, 2023. "Genome-wide screening in pluripotent cells identifies Mtf1 as a suppressor of mutant huntingtin toxicity," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    7. Zengpeng Han & Nengsong Luo & Wenyu Ma & Xiaodong Liu & Yuxiang Cai & Jiaxin Kou & Jie Wang & Lei Li & Siqi Peng & Zihong Xu & Wen Zhang & Yuxiang Qiu & Yang Wu & Chaohui Ye & Kunzhang Lin & Fuqiang X, 2023. "AAV11 enables efficient retrograde targeting of projection neurons and enhances astrocyte-directed transduction," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Rasmus Berglund & Yufei Cheng & Eliane Piket & Milena Z. Adzemovic & Manuel Zeitelhofer & Tomas Olsson & Andre Ortlieb Guerreiro-Cacais & Maja Jagodic, 2024. "The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Daniel Bormann & Michael Knoflach & Emilia Poreba & Christian J. Riedl & Giulia Testa & Cyrille Orset & Anthony Levilly & Andréa Cottereau & Philipp Jauk & Simon Hametner & Nadine Stranzl & Bahar Gola, 2024. "Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    10. Aletta M. R. Bosch & Marlijn Poel & Nina L. Fransen & Maria C. J. Vincenten & Anneleen M. Bobeldijk & Aldo Jongejan & Hendrik J. Engelenburg & Perry D. Moerland & Joost Smolders & Inge Huitinga & Jörg, 2024. "Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Hannah E. Salapa & Patricia A. Thibault & Cole D. Libner & Yulian Ding & Joseph-Patrick W. E. Clarke & Connor Denomy & Catherine Hutchinson & Hashim M. Abidullah & S. Austin Hammond & Landon Pastushok, 2024. "hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS)," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Manik Kuchroo & Marcello DiStasio & Eric Song & Eda Calapkulu & Le Zhang & Maryam Ige & Amar H. Sheth & Abdelilah Majdoubi & Madhvi Menon & Alexander Tong & Abhinav Godavarthi & Yu Xing & Scott Gigant, 2023. "Single-cell analysis reveals inflammatory interactions driving macular degeneration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39046-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.