A new type of cell supports remyelination

Epub ahead of printOlah et al. Identification of a microglia phenotype supportive of remyelination. Glia. 2011 Nov 9. doi: 10.1002/glia.21266. 

Background: In MS, oligodendrocyte precursor cells (OPCs), the cells that produce oligodendrcytes - which in turn make myelin - attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the MS lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia, an immune cell of the central nervous system, are known to play a central role in neuroinflammatory processes. 

Fig: Microglia stained using the silver method.
Aim: To investigate the microglia that supports remyelination, we performed genome-wide gene expression analysis of microglia from the corpus callosum (an important tract of fibres linking the two hemispheres of the brain) during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin-induced primary demyelination. 

Results: The investigators provide evidence for the existence of a specific subtype microglia that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis (ingestion) of myelin debris (damage myelin) and apoptotic cells (dead cells) during demyelination. Furthermore, they express a cytokine and chemokine repertoire (immune signalling molecules) enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support (growth factors) during remyelination. 

Conclusions: This study not only provides a detailed transcriptomic (gene product) analysis of the remyelination-supportive microglia type but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis (keeping the tissue healthy and in balance) and the support of regeneration already at the earliest stages in the development of demyelinating lesions. 

"This is a basic science experiment looking at the contribution of a specific cell in promoting remyelination. Is it important? Yes, I think so. If we can show that the same cells exist in humans and we can work-out how to stimulate these cells and enhance their function we may have a treatment that promotes remyelination. Experts in the field believe that remyelination is the best form of neuroprotection we have; if an axon or nerve fibre is demyelinated for too long it is destined to die. This is why we are desperate to get drugs that can protect the nerves from dying so remyelination can occur or to remyelinate them as soon as possible to stop them dying." 

"This study demonstrates why we need to invest in basic science; insights from basic biology underpins our understanding of biology and disease and eventually leads to the design of rational treatments."


CoI: Prof. Sandra Amor (2nd author) is a member of our group