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<p>Multiple sclerosis (MS) is a chronic, inflammatory condition characterized by neurodegeneration and lost myelin, or demyelination. This lost myelin may be regenerated in people with MS through a process called remyelination, that is prone to failure and is impaired with age. Remyelination is facilitated by microglia but our understanding of the microglial response during remyelination is incomplete. Here, we profile the microglial response during remyelination in the lysolecithin mouse model using single-cell RNA sequencing and find several distinct microglial states during the early stages of remyelination that coalesce into a resolved state defined by the presence of myelin transcripts, a state also present in MS brains. We also observe a delay in the appearance of several microglial states with age, in concordance with delayed remyelination. This multi-faceted microglial response during efficient remyelination provides the basis of multi-faceted microglia-specific targets for future MS therapies.</p>

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Age-impaired remyelination is associated with dysregulated microglial transitions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月12日

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  • Sameera Zia,
  • Marianela E. Traetta,
  • Charbel S. Baaklini,
  • Brady P. Hammond,
  • Rebecca K. John,
  • Katherine M. Souter,
  • Niels Meijns,
  • Larry K. A. Afun,
  • Sharmistha Panda,
  • Fernando González Ibáñez,
  • Mena K. Burr,
  • Eva Dhupia,
  • Abhisha M. Rathod,
  • Andre O. Faria,
  • Dhruvish Zaveri,
  • Sowmya Challa,
  • Eugene Hahn,
  • Sohrab B. Manesh,
  • Kelly V. Lee,
  • Madelene F. S. Ho,
  • Timothy N. Friedman,
  • Aislinn D. Maguire,
  • Arina Pang,
  • Olivia Farkas,
  • Bożena Szulc,
  • Luiz Tenorio,
  • Diya Vyas,
  • Olivia R. La Caprara,
  • Wolfram Tetzlaff,
  • Sarthak Sinha,
  • Gregory J. Duncan,
  • Anastassia Voronova,
  • Bradley J. Kerr,
  • Marie-Eve Tremblay,
  • Jeff Biernaskie,
  • Geert Schenk,
  • Jason R. Plemel

摘要

Multiple sclerosis (MS) is a chronic, inflammatory condition characterized by neurodegeneration and lost myelin, or demyelination. This lost myelin may be regenerated in people with MS through a process called remyelination, that is prone to failure and is impaired with age. Remyelination is facilitated by microglia but our understanding of the microglial response during remyelination is incomplete. Here, we profile the microglial response during remyelination in the lysolecithin mouse model using single-cell RNA sequencing and find several distinct microglial states during the early stages of remyelination that coalesce into a resolved state defined by the presence of myelin transcripts, a state also present in MS brains. We also observe a delay in the appearance of several microglial states with age, in concordance with delayed remyelination. This multi-faceted microglial response during efficient remyelination provides the basis of multi-faceted microglia-specific targets for future MS therapies.