Oligodendrocyte progenitor cell responses to inflammatory demyelination with aging in mouse model of multiple sclerosis

Abstract

Oligodendrocyte progenitor cells (OPCs) have the capacity to self-renew, differentiate, and remyelinate the CNS. Aging is associated with a reduction in the functional capacity of OPCs even in the absence of an autoimmune insult. To determine how aging affects the response of oligodendroglia to a strong inflammatory insult comparable to an immune-mediated demyelinating event in multiple sclerosis (MS), we performed adoptive transfer of young myelin-reactive Th17 T cells into young and aged OPC lineage tracing mice. After adoptive transfer, OPCs were enriched within spinal cord lesions of both young and aged mice. However differentiated oligodendrocytes (OLs) were significantly reduced after adoptive transfer. Both young and aged OPCs differentiated into mature OLs during adoptive transfer. Transmission electron microscopy revealed thinly myelinated axons without degenerative features that likely represent remyelinated axons in lesions of both age groups. Young and aged OPCs rise to the challenge after a strong auto-immune attack, suggesting that compensatory strategies permit both young and aged oligodendroglia to survive despite an inflammatory environment. Identifying pathways that promote resilience of oligodendroglia in the face of an inflammatory challenge will facilitate the development of remyelinating therapies for people with MS.