Cited by 69Autophagy in Disease and TherapyMultiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanisms

Autophagy Promotes Oligodendrocyte Survival and Function following Dysmyelination in a Long-Lived Myelin Mutant

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Smith, Chelsey M., Mayer, Joshua A., Duncan, Ian D.·2013·The Journal of Neuroscience

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.

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Crossref · 10.1523/jneurosci.0233-13.2013

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  • Autophagy activation enhances oligodendrocyte survival and promotes myelination in a rat model of demyelinating disease.

    “Consistent with these findings, autophagy activation enhances oligodendrocyte survival and promotes myelination in a rat model of demyelinating disease [448].”

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Authors
Smith, C. M., Mayer, J. A., & Duncan, I. D.
Affiliations
University of Wisconsin–Madison (US)
Venue
The Journal of Neuroscience
Published
2013-05-01
Volume
33
Issue
18
Pages
8088-8100
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2053863260
Cited by
69
References
54
Citations by year
2026: 4 · 2025: 2 · 2024: 4 · 2023: 9 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 9 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 9 · 2014: 5 · 2013: 2
FWCI
4.13
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (T32-GM007507)
  • Graduate Women in Science
  • National Institute of General Medical Sciences (T32GM007507)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
autophagy, oligodendrocyte survival, dysmyelination, demyelination, autophagosomes, lysosomes, intermittent fasting, myelination, myelin thickness
MeSH terms
Age Factors, Animals, Animals, Newborn, Autophagy, Bromodeoxyuridine, Cell Survival, Cells, Cultured, Chloroquine, Cytoplasm, Demyelinating Diseases, Myelin Basic Protein, Fasting, Female, Male, Microtubule-Associated Proteins, Mutation, Myelin Sheath, Oligodendroglia, Peptides, Rats, Mutant Strains, Spinal Cord, Up-Regulation, Myelin Proteolipid Protein, Rats, Long-Evans, Rats

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