Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation

By Mark Kotter, Wen-Wu Li, Chao Zhao, Robin J. M. Franklin. Journal of Neuroscience, 2006

731 citations recorded by the source corpus.

Demyelination in the adult CNS can be followed by extensive repair. However, in multiple sclerosis, the differentiation of oligodendrocyte lineage cells present in demyelinated lesions is often inhibited by unknown factors. In this study, we test whether myelin debris, a feature of demyelinated lesions and an in vitro inhibitor of oligodendrocyte precursor differentiation, affects remyelination efficiency. Focal demyelinating lesions were created in the adult rat brainstem, and the naturally generated myelin debris was augmented by the addition of purified myelin. After quantification of myelin basic protein mRNA expression from lesion material obtained by laser capture microdissection and supported by histological data, we found a significant impairment of remyelination, attributable to an arrest of the differentiation and not the recruitment of oligodendrocyte precursor cells. These data identify myelin as an inhibitor of remyelination as well as its well documented inhibition of axon regeneration.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/a750e9bf37bca79b038c847b4e661e9f3a37f22d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Robin J. M. Franklin
2. D. Rowitch

In Developmental Neuroscience

1. Mark Kotter
2. Robin J. M. Franklin
3. C. ffrench-Constant
4. Chao Zhao
5. D. Rowitch
6. C. Iadecola

Citations in the corpus

• Debris clearance by microglia: an essential link between degeneration and regeneration (2008, background): “…efficiency of remyelination and the effectiveness of myelin debris removal, both occurring in young animals more effectively than in older adult animals or young animals in which additional myelin was experimentally added (Shields et al., 1999; Kotter et al., 2005, 2006; Dubois-Dalcq et al., 2005).”
• Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. (2009, background): “…of a pathway might delay remyelination, it is overly simplistic to expect that inhibition of the same pathway would accelerate repair in the complex milieu of an MS lesion in which several inhibitory pathways might be active, compounded by the presence of myelin debris (Kotter et al. 2006).”
• Rejuvenation of regeneration in the aging central nervous system (2012, neutral): “Myelin contains proteins that inhibit OPC differentiation, and previous studies have highlighted the importance of macrophage-mediated removal of myelin debris in remyelination (Baer et al., 2009; Kotter et al., 2006).”
• Remyelination in the CNS: from biology to therapy (2008, background): “This is important because CNS myelin contains proteins that inhibit OPC differentiation both in vitro and during remyelinatio”