Lithium improves cell viability in psychosine-treated MO3.13 human oligodendrocyte cell line via autophagy activation

J Neurosci Res. 2016 Nov;94(11):1246-60. doi: 10.1002/jnr.23910.


Globoid cell leukodystrophy (GLD) is a rare, rapidly progressing childhood leukodystrophy triggered by deficit of the lysosomal enzyme galactosylceramidase (GALC) and characterized by the accumulation of galactosylsphingosine (psychosine; PSY) in the nervous system. PSY is a cytotoxic sphingolipid, which leads to widespread degeneration of oligodendrocytes and Schwann cells, causing demyelination. Here we report on autophagy in the human oligodendrocyte cell line MO3.13 treated with PSY and exploitation of Li as an autophagy modulator to rescue cell viability. We demonstrate that PSY causes upregulation of the autophagic flux at the level of autophagosome and autolysosome formation and LC3-II expression. We show that pretreatment with Li, a drug clinically used to treat bipolar disorders, can further stimulate autophagy, improving cell tolerance to PSY. This Li protective effect is found not to be linked to reduction of PSY-induced oxidative stress and might not stem from a reduction of PSY accumulation. These data provide novel information on the intracellular pathways activated during PSY-induced toxicity and suggest the autophagy pathway as a promising novel therapeutic target for ameliorating the GLD phenotype. © 2016 Wiley Periodicals, Inc.

Keywords: MO3.13 cell line; autophagy; galactosylceramidase; globoid cell leukodystrophy; krabbe; lithium; oligodendrocyte cell line; psychosine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Annexin A5 / metabolism
  • Autophagy / drug effects*
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Lactosylceramides / genetics
  • Lactosylceramides / metabolism
  • Lithium / pharmacology*
  • Oligodendroglia / drug effects*
  • Psychosine / metabolism
  • Psychosine / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Sequestosome-1 Protein / metabolism
  • Signal Transduction / drug effects
  • Transfection
  • Tubulin / genetics
  • Tubulin / metabolism


  • Annexin A5
  • Lactosylceramides
  • Reactive Oxygen Species
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Tubulin
  • Green Fluorescent Proteins
  • Psychosine
  • lactotriaosylceramide
  • Lithium