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dc.contributor.authorJourdain, P.
dc.contributor.authorAllaman, I.
dc.contributor.authorRothenfusser, K.
dc.contributor.authorFiumelli, Hubert
dc.contributor.authorMarquet, P.
dc.contributor.authorMagistretti, Pierre J.
dc.date.accessioned2016-02-21T10:25:03Z
dc.date.available2016-02-21T10:25:03Z
dc.date.issued2016-02-19
dc.identifier.citationL-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade 2016, 6:21250 Scientific Reports
dc.identifier.issn2045-2322
dc.identifier.pmid26893204
dc.identifier.doi10.1038/srep21250
dc.identifier.urihttp://hdl.handle.net/10754/596851
dc.description.abstractConverging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.urlhttp://www.nature.com/articles/srep21250
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.titleL-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalScientific Reports
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionBrain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
dc.contributor.institutionCentre de Neurosciences Psychiatriques, CHUV, Département de Psychiatrie, Site de Cery, CH-1008 Prilly/Lausanne, Switzerland
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personFiumelli, Hubert
kaust.personMagistretti, Pierre J.
refterms.dateFOA2018-06-13T15:22:00Z
dc.date.published-online2016-02-19
dc.date.published-print2016-08


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