Lithium improves cell viability in psychosine‐treated MO3.13 human oligodendrocyte cell line via autophagy activation. Issue 11 (November 2016)

• Record Type: Journal Article
• Authors: Del Grosso, Ambra; Antonini, Sara; Angella, Lucia; Tonazzini, Ilaria; Signore, Giovanni; Cecchini, Marco
• Other Names: Bongarzone Ernesto R. guestEditor.
• Is Part Of: Journal of neuroscience research. Volume 94:Issue 11(2016)
• Page Start: 1246
• Page End: 1260
• Publication Date: 2016-11
• Subjects: galactosylceramidase -- lithium -- autophagy -- oligodendrocyte cell line -- MO3.13 cell line -- psychosine -- krabbe -- globoid cell leukodystrophy; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.23910
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract : 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. Abstract : The authors 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 and demonstrate that PSY causes upregulation of the autophagic flux at the level of autophagosome and autolysosome formation and LC3‐II expression.