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The Metabolic Disturbances of Motoneurons Exposed to Glutamate

  • Blandine Madji Hounoum
  • Hélène Blasco
  • Emmanuelle Coque
  • Patrick Vourc’h
  • Patrick Emond
  • Philippe Corcia
  • Christian R. Andres
  • Cédric Raoul
  • Sylvie Mavel
Article

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.

Keywords

Fingerprinting Excitotoxicity Metabolomics Amyotrophic lateral sclerosis ALS Primary motoneuron cultures Astrocytes Metabolites 

Notes

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.

Author 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.

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).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2018_945_MOESM1_ESM.docx (592 kb)
ESM 1 (DOCX 591 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Blandine Madji Hounoum
    • 1
  • Hélène Blasco
    • 1
    • 2
  • Emmanuelle Coque
    • 3
  • Patrick Vourc’h
    • 1
    • 2
  • Patrick Emond
    • 1
  • Philippe Corcia
    • 1
    • 4
  • Christian R. Andres
    • 1
    • 2
  • Cédric Raoul
    • 3
  • Sylvie Mavel
    • 1
    • 5
  1. 1.INSERM U930 “Imagerie et Cerveau,” CHRU de ToursUniversité François-RabelaisToursFrance
  2. 2.Laboratoire de Biochimie et de Biologie MoléculaireHôpital Bretonneau, CHRU de ToursToursFrance
  3. 3.The Institute for Neurosciences of Montpellier, Inserm UMR1051Univ Montpellier, Saint Eloi HospitalMontpellierFrance
  4. 4.Centre SLA, Service de Neurologie, CHRU de ToursToursFrance
  5. 5.UFR PharmacieToursFrance

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