Friday, 24 October 2014

What remyelinates

Xing YL, Röth PT, Stratton JA, Chuang BH, Danne J, Ellis SL, Ng SW, Kilpatrick TJ, Merson TD. Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination. J Neurosci. 2014 ;34(42):14128-46.

Parenchymal oligodendrocyte progenitor cells (pOPCs) are considered the principal cell type responsible for oligodendrogenesis and remyelinaton in demyelinating diseases. Recent studies have demonstrated that neural precursor cells (NPCs) from the adult subventricular zone (SVZ) can also generate new oligodendrocytes after demyelination. However, the relative contribution of NPCs versus pOPCs to remyelination is unknown. 


We used in vivo genetic fate mapping to assess the behavior of each progenitor type within the corpus callosi (CCs) of mice subjected to cuprizone-induced demyelination. Nestin-CreER(T2) and Pdgfra-CreER(T2) transgenic mice were crossed with fluorescent Cre reporter strains to map the fate of NPCs and pOPCs respectively. In cuprizone-challenged mice, substantial numbers of NPCs migrated into the demyelinated CC and contributed to oligodendrogenesis. This capacity was most prominent in rostral regions adjacent to the SVZ where NPC-derived oligodendrocytes significantly outnumbered those generated from pOPCs. Sixty-two percent of all nodes of Ranvier in this region were flanked by at least one paranode generated from an NPC-derived oligodendrocyte. Remarkably, g-ratios (ratio of the axon diameter to the diameter of the axon plus myelin sheath) of myelinated axons in regions subject to significant NPC-derived remyelination were equivalent to those of unchallenged controls, and immunoelectron microscopy revealed that NPC-derived myelin was significantly thicker than that generated by pOPCs, regardless of axonal caliber. We also demonstrate that a reduced efficiency of remyelination in the caudal CC was associated with long-term impairment in the maturation of oligodendrogenic NPCs but only transient delay in pOPC differentiation. Collectively, our data define a major distinct role for NPCs in remyelination, identifying them as a key target for enhancing myelin repair in demyelinating diseases.

You can all read the post. It is typically stated that remyelination produces thinner myelin so the D above would be less and the g would therefore be bigger. In this instance there was normal myelination

2 comments:

  1. Attention:
    Professor Gavin Giovannoni:



    Simpe Question to Professor Gavin Giovannoni:

    You mentionjed in an earlier statement in this blog, that you are involved in a study with an agent called laquinimod in progressive MS.

    Also, there have been some Buzz avbout this study in general among the MS community, fueled by, for instance, this PDF file that presents the rationale for laquinimod in Porgressive MS.

    http://www.projectsinknowledge.com/Activity/pdfs/2181.01.pdf


    I Think it was presented during AAN 2014.

    Questions I urgently would be most obliged if Professor Gavin Giovannoni:could address :
    1.
    Will or has this study started or has it been canceled.
    2.
    Given that it will start, what are the possibilities to participate if you live in Denmark ?

    Please advice most urgently

    Anne in Copenhagen

    ReplyDelete
  2. IGF-1 shown to induce NPCs differentiation into oligos. Interestingly IGF-1 levels are lower after immunodepleting therapies then in controls and prior to therapy. Just wonder why nobody tried HGH in MS

    ReplyDelete

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