Young and old oligodendroglial function in inflammatory models
Multiple sclerosis (MS) is a chronic demyelinating, inflammatory, and neurodegenerative disease of the central nervous system. Remyelinating is a regenerative process by which oligodendrocytes restore myelin sheaths to damaged axons. Single-cell sequencing of oligodendroglia in inflammatory mouse models (active experimental autoimmune encephalomyelitis) and human MS tissue has revealed that subclusters of oligodendroglia with immunoregulatory transcripts are enriched and may persist in the setting of inflammation. The role and functional capabilities of these immune oligodendroglia or iOPC/iOL (immune oligodendrocyte progenitor cell or immune oligodendrocyte) are unknown. Immunoregulatory molecules expressed by iOPC/iOL may perpetuate inflammation and contribute to cell death and/or and dampen inflammatory activity, and promote iOPC/iOL survival.
Aging is correlated with MS progression and neurodegeneration. Prior work in toxin-mediated and mouse models indicates that aging can influence oligodendroglial properties and negatively impact remyelination. How aging impacts oligodendroglial function and heterogeneity in an inflammatory mouse model is unknown.
The long-term goal of this research is to better understand oligodendroglial properties in the context of inflammation and aging in order to drive the development of therapeutic targets to promote remyelination and repair in relapsing and progressive MS.
Aims of the aging inflammatory oligodendroglial project are focused on:
- Determining how aging impacts oligodendroglial survival, differentiation, remyelination and transcriptional heterogeneity in the Th17 adoptive transfer model
- Manipulation of pathways of interest in the Th17 adoptive transfer and cuprizone models that we hypothesize promote oligodendroglial survival in the context of inflammation
Techniques utilized in the Harrington lab include:
T cell adoptive transfer models, active immunization models, cuprizone model, flow cytometry, immunohistochemistry, RNAscope, single cell RNA sequencing, oligodendroglial culture, T cell culture, electron microscopy, epifluorescence and confocal microscopy, and CRISPR gene editing.
