Age-impaired remyelination is associated with dysregulated microglial transitions

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

Nature Communications, 2025, vol. 16, issue 1, 1-24

Abstract: Abstract 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64906-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64906-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64906-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().