Saturday, 9 February 2013

Demyelinated nerves can survive for some time

Smith et al. Myelin Loss Does Not Lead to Axonal Degeneration in a Long-Lived Model of Chronic DemyelinationThe Journal of Neuroscience, 2013, 33(6):2718-2727; doi:10.1523/JNEUROSCI.4627-12.2013

Background: Current dogma suggests that chronically demyelinated axons are at risk for degeneration, with axonal loss resulting in permanent disability in myelin disease. However, the trophic role of the myelin sheath in long-term axonal survival is incompletely understood. Previous observations of the effect of dysmyelination or demyelination on axonal survival in the myelin mutants has been limited because of their short life span. 


Methods and results: In this study, we used the Long–Evans shaker (les) rat, which can live up to 9 months, to study axonal health and survival after chronic demyelination. At 2 weeks, ∼29% of medium and ∼47% of large fibre axons are myelinated in les spinal cord. However, by 3 months, no medium and ∼<1% of large-diameter axons retain myelin. After demyelination, axons have a reduced-caliber, abnormal neurofilament distribution and an increase in mitochondrial number. However, there are no signs of axonal degeneration in les rats up to 9 months. Instead, there is a profound increase in oligodendrocytes, which were found to express BDNF, NT-3, and IGF-1. 

Conclusion: Importantly, this study provides in vivo evidence that mature glial cells produce various neurotrophic factors that may aid in the survival of axons after chronic demyelination.


Myelin staining a 5–6 month old wild-type (WT, left panels) and les rat.. They shows prominent myelin labeling in the WT rat (A/C) with no detectable myelin staining in the les rat (B/D).

It is not just dogma, but has been shown that in many different situations that loss of myelin can make nerves vulnerable to damage, However, it also seems clear that this is a slow process and demyelinated nerves do survive for some time, otherwise the pathologists would have seen that all demyelinated nerves would have markers of death induction. However, it is also the case that many of the dymyelinating or dysmyelinating mutants get neurological conditions and die. These include naturally occurring mutants such as Jimpy, Shiverer mice and Shaking pup animals, Taiep rat. The Long –evans shaker survive for some time and get demyelinated nerves.and so have adapted to this effect and the study indicates that these rats produce a number of nerve growth factors that may aid this. These obviously provide routes to help support demyelinated nerves that are clearly are present in MSers.

4 comments:

  1. Interesting, is it possible in vivo to determine whether axon loss has occured and thus if not give hope that some funtion can return ? Or is that stuff dreams are made of? Btw nice to meet you at the research day,I had met you and Prof G before but Mouse Dr2 I hadn't. Can I say he wasn't a bit like I imagined, nose and ears yes, but his tail was much shorter than expected.

    Regards as always

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  2. It is possible using MRI to look for axon loss you canfollow nerve tracts but if you can do electrophysiology, this is notalways possible, you can also get an idea of whats there. They are improving imaging techniques all the time but conventional MRI does not have the resolution of the microscope.

    MD2 Tail shorter but the alter ego has more bite

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  3. The important thing to note here is that this model has only partial relevance to MS. This is a study in myelin deficient mutant rats and there is no inflammatory component as seen in MS. It may be that the presence of inflammatory cells may be important in finishing off the nerves, this is missing in this study. So a demyelinated nerve may be able to survive a long time as long as nothing else happens but it may be a very diferent story once inflammatory cells arrive on the scene.
    I wonder if it is possible to induce EAE in these rats and if the nerve loss would be accelerated if you did?

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    Replies
    1. Interesting experiment sensitise to non myelin antigen

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