The Age-Related Decrease in CNS Remyelination Efficiency Is Attributable to an Impairment of Both Oligodendrocyte Progenitor Recruitment and Differentiation
By F. Sim, Chao Zhao, J. Penderis, Robin J. M. Franklin. Journal of Neuroscience, 2002
619 citations recorded by the source corpus.
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-α 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.
Subfields: Cancer Research, Developmental Neuroscience, Neurology
View Paper: https://www.semanticscholar.org/paper/754f50dfc9adf3b233b058ea7bc5e4beb664e84c
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Citations in the corpus
- CNS-Resident Glial Progenitor/Stem Cells Produce Schwann Cells as well as Oligodendrocytes during Repair of CNS Demyelination (2010, neutral): “SCIP is expressed by premyelinating Schwann cells and its expression is downregulated at the onset of myelination (Sim et al., 2002a).”
- Debris clearance by microglia: an essential link between degeneration and regeneration (2008, background): “Furthermore, older rats compared to young rats showed delayed recruitment of phagocytic cells and less clearance of myelin after a toxin-induced demyelination lesion (Zhao et al., 2006), which correlates with the slower remyelination in older animals (Sim et al., 2002).”
- Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation (2006, methodology): “Remyelination of ethidium bromide-induced demyelination is mediated by OPCs that are recruited into the area of demyelination and that subsequently differentiate into remyelinating oligodendrocytes (Sim et al., 2002b; Fancy et al., 2004).”
- Remyelination in the CNS: from biology to therapy (2008, background): “; and second, that remyelination occurs in areas that have been experimentally depleted of oligodendrocyte”
- Rejuvenation of regeneration in the aging central nervous system (2012, neutral): “However, like most mammalian tissues, the CNS experiences declining efficiency of regeneration with increasing age (Sim et al., 2002).”