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The Metabolic Disturbances of Motoneurons Exposed to Glutamate

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Abstract

Glutamate-induced excitotoxicity is considered as one of the major pathophysiological factors of motoneuron death in amyotrophic lateral sclerosis and other motoneuron diseases. In order to expand our knowledge on mechanisms of glutamate-induced excitotoxicity, the present study proposes to determine the metabolic consequences of glutamate and astrocytes in primary enriched motoneuron culture. Using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), we showed that the presence of astrocytes and glutamate profoundly modified the metabolic profile of motoneurons. Our study highlights for the first time that crosstalk between astrocytes and enriched motoneuron culture induced alterations in phenylalanine, tryptophan, purine, arginine, proline, aspartate, and glutamate metabolism in motoneurons. We observed that astrocytes modulate the sensitivity of motoneurons to glutamate, since metabolites altered by glutamate in motoneurons cultured alone were different (except 5-hydroxylysine) from those altered in co-cultured motoneurons. Our findings provide new insight into the metabolic alterations associated to astrocytes and glutamate in motoneurons and provide opportunities to identify novel therapeutic targets.

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Acknowledgments

We thank the staff of the Programme Pluri-Formation “Analyze des Systèmes Biologiques” (PPF ASB) platform of the University François-Rabelais in Tours, France, Céline Salsac, and Antoine Lefèvre for technical assistance.

Funding

This work was supported by grants from the institut national de la santé et de la recherche médicale (INSERM), the association française pour la recherche sur la SLA (ARSLA), ANR-14-RARE-0006 E-RARE “FasSMALS” and ANR “GliALS”. E.C. received a grant from the association française contre les myopathies (AFM) and B. MH received a grant from “La Région Centre” (2013–10).

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Author notes

  1. Hélène Blasco and Sylvie Mavel contributed equally to this work.

Authors and Affiliations

  1. INSERM U930 “Imagerie et Cerveau,” CHRU de Tours, Université François-Rabelais, Tours, France

    Blandine Madji Hounoum, Hélène Blasco, Patrick Vourc’h, Patrick Emond, Philippe Corcia, Christian R. Andres & Sylvie Mavel

  2. Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Bretonneau, CHRU de Tours, Tours, France

    Hélène Blasco, Patrick Vourc’h & Christian R. Andres

  3. The Institute for Neurosciences of Montpellier, Inserm UMR1051, Univ Montpellier, Saint Eloi Hospital, Montpellier, France

    Emmanuelle Coque & Cédric Raoul

  4. Centre SLA, Service de Neurologie, CHRU de Tours, Tours, France

    Philippe Corcia

  5. UFR Pharmacie, INSERM U930, 31 av Monge, 37200, Tours, France

    Sylvie Mavel

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  1. Blandine Madji Hounoum
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  2. Hélène Blasco
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Contributions

B. MH, H. B, E. C, P. V, P. E, P. C, C. R. A, C. R, and S. M designed of the experiments and wrote the manuscript. H. B and S. M managed the project. B. MH, E. C, C. R, and S. M performed experiments and/or contributed to the interpretation of data.

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Correspondence to Sylvie Mavel.

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Madji Hounoum, B., Blasco, H., Coque, E. et al. The Metabolic Disturbances of Motoneurons Exposed to Glutamate. Mol Neurobiol 55, 7669–7676 (2018). https://doi.org/10.1007/s12035-018-0945-8

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