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Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling
- Source :
- Glia. 65:592-605
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non-cell-autonomous effects of astrocytes. However, mechanisms underlying astrocyte-mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS-associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS-causing mutated superoxide dismutase-1 (SOD1) when co-cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra- and intra-cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592-605.
- Subjects :
- 0301 basic medicine
Superoxide
SOD1
Excitotoxicity
Glutamate receptor
Neurotoxicity
Biology
medicine.disease_cause
medicine.disease
03 medical and health sciences
Cellular and Molecular Neuroscience
Metabolic pathway
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
nervous system
Neurology
chemistry
medicine
Amyotrophic lateral sclerosis
Neuroscience
030217 neurology & neurosurgery
Astrocyte
Subjects
Details
- ISSN :
- 08941491
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Glia
- Accession number :
- edsair.doi...........bb2ad4a45cc75a8f6b6b1458bc00717d