Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.

TitleAutophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.
Publication TypeJournal Article
Year of Publication2013
AuthorsSmith CM, Mayer JA, Duncan ID
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume33
Issue18
Pagination8088-100
Date Published2013 May 1
Abstract

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.

DOI10.1093/jac/dkt230
Alternate JournalJ. Neurosci.