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Regulation of stress granule formation in human oligodendrocytes

Author

Listed:
  • Florian Pernin

    (McGill University)

  • Qiao-Ling Cui

    (McGill University)

  • Abdulshakour Mohammadnia

    (McGill University)

  • Milton G. F. Fernandes

    (McGill University)

  • Jeffery A. Hall

    (McGill University Health Centre)

  • Myriam Srour

    (Montreal Children’s Hospital)

  • Roy W. R. Dudley

    (Montreal Children’s Hospital)

  • Stephanie E. J. Zandee

    (Centre de Recherche Hospitalier de l’Université de Montréal)

  • Wendy Klement

    (Centre de Recherche Hospitalier de l’Université de Montréal)

  • Alexandre Prat

    (Centre de Recherche Hospitalier de l’Université de Montréal)

  • Hannah E. Salapa

    (University of Saskatchewan)

  • Michael C. Levin

    (University of Saskatchewan)

  • G. R. Wayne Moore

    (McGill University)

  • Timothy E. Kennedy

    (McGill University)

  • Christine Vande Velde

    (Centre de Recherche Hospitalier de l’Université de Montréal)

  • Jack P. Antel

    (McGill University)

Abstract

Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45746-6
    DOI: 10.1038/s41467-024-45746-6
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