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.