Altered metabolic profiles associate with toxicity in SOD1G93A astrocyte-neuron co-cultures

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Title: Altered metabolic profiles associate with toxicity in SOD1G93A astrocyte-neuron co-cultures
Author(s): Valbuena, GN
Tortarolo, M
Bendotti, C
Cantoni, L
Keun, HC
Item Type: Journal Article
Abstract: Non-cell autonomous processes involving astrocytes have been shown to contribute to motor neuron degeneration in amyotrophic lateral sclerosis. Mutant superoxide dismutase 1 (SOD1G93A) expression in astrocytes is selectively toxic to motor neurons in co-culture, even when mutant protein is expressed only in astrocytes and not in neurons. To examine metabolic changes in astrocyte-spinal neuron co-cultures, we carried out metabolomic analysis by 1H NMR spectroscopy of media from astrocyte-spinal neuron co-cultures and astrocyte-only cultures. We observed increased glucose uptake with SOD1G93A expression in all co-cultures, but while co-cultures with only SOD1G93A neurons had lower extracellular lactate, those with only SOD1G93A astrocytes exhibited the reverse. Reduced branched-chain amino acid uptake and increased accumulation of 3-methyl-2-oxovalerate were observed in co-culture with only SOD1G93A neurons while glutamate was reduced in all co-cultures expressing SOD1G93A. The shifts in these coupled processes suggest a potential block in glutamate processing that may impact motor neuron survival. We also observed metabolic alterations which may relate to oxidative stress responses. Overall, the different metabolite changes observed with the two SOD1G93A cell types highlight the role of the astrocyte-motor neuron interaction in the resulting metabolic phenotype, requiring further examination of altered metabolic pathways and their impact on motor neuron survival.
Publication Date: 3-Mar-2017
Date of Acceptance: 27-Jan-2017
URI: http://hdl.handle.net/10044/1/44250
DOI: https://dx.doi.org/10.1038/s41598-017-00072-4
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Copyright Statement: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 259867
Publication Status: Published
Article Number: 50
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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