Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures

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...

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Autores principales:	Gabriel N. Valbuena, Massimo Tortarolo, Caterina Bendotti, Lavinia Cantoni, Hector C. Keun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba9554b5484c44d4be33b5d7672298cf
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spelling	oai:doaj.org-article:ba9554b5484c44d4be33b5d7672298cf2021-12-02T12:32:30ZAltered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures10.1038/s41598-017-00072-42045-2322https://doaj.org/article/ba9554b5484c44d4be33b5d7672298cf2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00072-4https://doaj.org/toc/2045-2322Abstract 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 met abolic pathways and their impact on motor neuron survival.Gabriel N. ValbuenaMassimo TortaroloCaterina BendottiLavinia CantoniHector C. KeunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gabriel N. Valbuena Massimo Tortarolo Caterina Bendotti Lavinia Cantoni Hector C. Keun Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
description	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 met abolic pathways and their impact on motor neuron survival.
format	article
author	Gabriel N. Valbuena Massimo Tortarolo Caterina Bendotti Lavinia Cantoni Hector C. Keun
author_facet	Gabriel N. Valbuena Massimo Tortarolo Caterina Bendotti Lavinia Cantoni Hector C. Keun
author_sort	Gabriel N. Valbuena
title	Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
title_short	Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
title_full	Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
title_fullStr	Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
title_full_unstemmed	Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
title_sort	altered metabolic profiles associate with toxicity in sod1g93a astrocyte-neuron co-cultures
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ba9554b5484c44d4be33b5d7672298cf
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Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures

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