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Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.
|Title||Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Smith CM, Mayer JA, Duncan ID|
|Journal||The Journal of neuroscience : the official journal of the Society for Neuroscience|
|Date Published||2013 May 1|
The Long-Evans shaker (les) rat has a mutation in myelin basic protein that results in severe CNS dysmyelination and subsequent demyelination during development. During this time, les oligodendrocytes accumulate cytoplasmic vesicles, including lysosomes and membrane-bound organelles. However, the mechanism and functional relevance behind these oligodendrocyte abnormalities in les have not been investigated. Using high-magnification electron microscopy, we identified the accumulations in les oligodendrocytes as early and late autophagosomes. Additionally, immunohistochemistry and Western blots showed an increase in autophagy markers in les. However, autophagy did not precede the death of les oligodendrocytes. Instead, upregulating autophagy promoted membrane extensions in les oligodendrocytes in vitro. Furthermore, upregulating autophagy in les rats via intermittent fasting increased the proportion of myelinated axons as well as myelin sheath thickness in les and control rats. Overall, this study provides insight into the abnormalities described in les as well as identifying a novel mechanism that promotes the survival and function of oligodendrocytes.
|Alternate Journal||J. Neurosci.|