Potential role of iron in repair of inflammatory demyelinating lesions.
Publication/Presentation Date
10-1-2019
Abstract
Inflammatory destruction of iron-rich myelin is characteristic of multiple sclerosis (MS). Although iron is needed for oligodendrocytes to produce myelin during development, its deposition has also been linked to neurodegeneration and inflammation, including in MS. We report perivascular iron deposition in multiple sclerosis lesions that was mirrored in 72 lesions from 13 marmosets with experimental autoimmune encephalomyelitis. Iron accumulated mainly inside microglia/macrophages from 6 weeks after demyelination. Consistently, expression of transferrin receptor, the brain's main iron-influx protein, increased as lesions aged. Iron was uncorrelated with inflammation and postdated initial demyelination, suggesting that iron is not directly pathogenic. Iron homeostasis was at least partially restored in remyelinated, but not persistently demyelinated, lesions. Taken together, our results suggest that iron accumulation in the weeks after inflammatory demyelination may contribute to lesion repair rather than inflammatory demyelination per se.
Volume
129
Issue
10
First Page
4365
Last Page
4376
ISSN
1558-8238
Published In/Presented At
Lee, N. J., Ha, S. K., Sati, P., Absinta, M., Nair, G., Luciano, N. J., Leibovitch, E. C., Yen, C. C., Rouault, T. A., Silva, A. C., Jacobson, S., & Reich, D. S. (2019). Potential role of iron in repair of inflammatory demyelinating lesions. The Journal of clinical investigation, 129(10), 4365–4376. https://doi.org/10.1172/JCI126809
Disciplines
Medicine and Health Sciences
PubMedID
31498148
Department(s)
Department of Medicine
Document Type
Article