Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures.
Sci Rep
; 7(1): 50, 2017 03 03.
Article
em En
| MEDLINE
| ID: mdl-28246392
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Astrócitos
/
Superóxido Dismutase-1
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Esclerose Lateral Amiotrófica
/
Neurônios Motores
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article