Basic Science: More clues for targets for remyelination

Chung AY et al. Microarray Screening for Genes Involved in Oligodendrocyte Differentiation in the Zebrafish CNS. Exp Neurobiol 2011 ;20:85-91.

Within the vertebrate nervous system, myelination is required for the normal function of neurons (nerves) by facilitating the rapid conduction of action potentials (nerve impulses) along axons. Oligodendrocytes (myelin-forming cells) are glial cells which myelinate axons in the central nervous system. Disruption of myelination and remyelination failure occur in diseases such as multiple sclerosis.
Despite the importance of myelination, the molecular basis of oligodendrocyte differentiation (generation of oligodendrocytes from more immature cells) and myelination are still poorly understood. To understand the molecular mechanisms which regulate oligodendrocyte differentiation and myelination, novel genes were identified using a microarray analysis (this looks for the genetic messages that are switched on to make proteins that are required for the function of the cells being analysed) . The analysis used oligodendrocyte lineage cells isolated from transgenic zebrafish expressing fluorescent (glow-in-the dark) proteins in the oligodendrocyte (myelin-forming cell) lineage cells. Seven genes (“I think it is not worth talking about these yet as it is too early”)not previously known to be involved in oligodendrocyte differentiation were identified, and their expression during oligodendrocyte development was validated.

Zebrafish are model organisms that the scientific community use to study genes and development (How we go from a fertilised egg to make the adult). They have young that are transparent and so by shining ulta violet light onto the genetically engineered-fish, then you can see when the flourescent (glow-in the dark) proteins indicating that myelination (in the case above) is occurring. You can then hunt to see which proteins are switched on using a process called micro array analysis, which looks for the messages that tell proteins to be produced.

Nerve cell bodies (nerve heads green) and axons (nerve bodies red) in a fish head.

This study has identified new molecules in addition to those known to be involved in the production of myelin. The more boffins know about this, the more likely that we will be able to develop drugs to help stimulate remyelination. So as you can see not all research involves mice. However this information is some way off leading to treatments and we need to ensure that these new targets are involved in myelination and importantly remyelination by human cells.

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  • Hmm, I suppose the long wait will be eventually worth it. I just hope I'm still well enough to benefit from the medication that promotes remyelination when it eventually gets to market, that is if I've still got any axons left by then.

    I hope that you will discuss such issues at your MS Open Day. Also, please film the talks and upload them because I live too far away to attend.

  • Re "…this information is some way off leading to treatments."

    Any idea how far off we are? A ball park figure perhaps?

  • "How far off"

    Dear Anon 12:00
    It depends on what the targets are and whether there are useful drugs and whether that have already been in humans but if you start from scratch which some of them will be it is at least 10-15years. Please see the posts "Drug the Game" to explain.

    However, there are some treatments in phase I that could mean a year or two, if you are on trial and a few years again after that.

    Some stem cells studies are ready to go.

    We may get good at detecting ways to see repair that could cut the trial time span very significantly as remyelination only takes a few weeks in animals.

    I know it won't be fast enough.

    Dear Anon 6:06
    Sorry that you can't make the open day but the talks will be filmed as they have been in the past.

    See the posts upto christmas for some of the subject matters. Remeber we can't necessarily cover all bases as we will focus on the stuff we are doing but will also give some breadth

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