Remyelination and minocycline

Epub: Tanaka et al. Minocycline reduces remyelination by suppressing ciliary neurotrophic factor expression after cuprizone-induced demyelination. J Neurochem. 2013 May 7.

Remyelination is disrupted in demyelinating diseases such as MS, but the underlying pathogenetic mechanisms are unclear. In this study, we employed the murine cuprizone model of demyelination, in which remyelination occurs after removal of the toxin from the diet, to examine the cellular and molecular changes during demyelination and remyelination. Microglia accumulated in the corpus callosum during weeks 2-4 of the cuprizone diet, and these cells remained activated 2 weeks after the change to the normal diet. To examine the role of microglia in remyelination, mice were treated with minocycline to inactivate these cells after cuprizone-induced demyelination. Minocycline treatment reduced the number of CC1-positive oligodendrocytes, as well as levels of MBP and CNPase in the remyelination phase. The expression of CNTF mRNA in the corpus callosum increased after 4 weeks on the cuprizone diet and remained high 2 weeks after the change to the normal diet. Minocycline suppressed CNTF expression during the remyelination phase on the normal diet. Primary culture experiments showed that CNTF was produced by microglia in addition to astrocytes. In vitro, CNTF directly affected the differentiation of oligodendrocytic cells. These findings suggest that minocycline reduces remyelination by suppressing CNTF expression by microglia after cuprizone-induced demyelination.

Minocycline is an antibiotic that inhibits microglial function. Some therefore hope that it will be beneficial, However if microglia are good cops then blocking their function would not be a good thing. This study suggests that it could block the production of a nerve growth factor.

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  • I thought minocycline had been proposed by some to be given as a course of treatment when you have a CIS? Also I think there's a Canadian study into giving it with GA, which showed a reduction in lesions. Minocycline is on the MS Soc website as a future possible treatment. Is it or isn't it any good?

  • Yes there are a number of studies in MS

    It is hard for me to say good or bad. On balance maybe good, but this goes to show what is good for the goose is not always good for the gander.

    For many years people have been talking about the anti-inflammatory effect of minocycline. However we know that some element of inflammation is important for clearing up debris and this promotes remyelination. Maybe this is what happens here. If you dont get the lesions you do not need to clear up damage

    This is why you need to see a a big picture as MS, it is not just about immune response.

    Likewise for the remyelinators they need to think outside of remyelination. Many of the target molecules to promote remyelination are commonly used elsewhere in other systems. Therefore their blockage could have side effects.

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