The age‐related decrease in CNS remyelination efficiency is caused by an impairment of both oligodendrocyte progenitor recruitment and differentiation

Abstract

Developing strategies to reverse the age‐associated decline in CNS remyelination requires the identification of how the regenerative process is impaired. We have addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, an impairment of OP differentiation into remyelinating oligodendrocytes. The OP response during remyelination of focal, toxin‐induced CNS demyelination in young and old rats was compared by in situ hybridization using probes to PGDF‐αR, and the OP transcription factor, MyT1. The expression patterns for both OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared to young. By comparing the mRNA expression pattern MyT1 with that of the myelin proteins MBP and Gtx, we have found that in the old animals there is also a delay in OP differentiation, which increases with longer survival times. These results indicate that the age‐associated decrease in remyelination efficiency occurs because of an impairment of OP recruitment and their subsequent differentiation into remyelinating oligodendrocytes, and that strategies aimed at ameliorating the age‐associated decline in remyelination efficiency will therefore need to promote both components of the regenerative process.