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The Journal of Neuroscience, April 1, 2002, 22(7):2451-2459
The Age-Related Decrease in CNS Remyelination Efficiency Is Attributable to an Impairment of Both Oligodendrocyte Progenitor Recruitment and Differentiation
Fraser J. Sim1, 2, Chao Zhao1, Jacques Penderis1, 3, and Robin J. M. Franklin1 1 Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom, 2 Department of Anatomy, University of Cambridge, Cambridge, CB2 3DY, United Kingdom, 3 Animal Health Trust, Kentford, Newmarket CB8 7UU, United Kingdom
The age-associated decrease in the efficiency of CNS remyelination has clear implications for recovery from demyelinating diseases such as multiple sclerosis (MS) that may last for several decades. Developing strategies to reverse the age-associated decline requires the identification of how the regenerative process is impaired. We addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, as is the case in some MS lesions, 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 two OP-expressed mRNA species: platelet-derived growth factor-
receptor and the OP transcription factor myelin transcription factor 1 (MyT1). We found that the expression patterns for the two OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared with the young animals. By comparing the mRNA expression pattern of MyT1 with that of the myelin proteins myelin basic protein and Gtx, we found that in the old animals there is also a delay in OP differentiation that 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 the subsequent differentiation of the OPs 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.
Key words: aging; demyelination; remyelination; in situ hybridization; oligodendrocyte progenitor; myelin transcription factor 1; platelet-derived growth factor receptor
Copyright © 2002 Society for Neuroscience 0270-6474/02/2272451-09$05.00/0
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