Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

Handle URI:
http://hdl.handle.net/10754/563661
Title:
Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
Authors:
Yang, Jiangyan; Ruchti, Evelyne; Petit, Jean Marie; Jourdain, Pascal; Grenningloh, Gabriele; Allaman, Igor; Magistretti, Pierre J. ( 0000-0002-6678-320X )
Abstract:
L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program
Publisher:
Proceedings of the National Academy of Sciences
Journal:
Proceedings of the National Academy of Sciences
Issue Date:
28-Jul-2014
DOI:
10.1073/pnas.1322912111
PubMed ID:
25071212
PubMed Central ID:
PMC4143009
Type:
Article
ISSN:
00278424
Sponsors:
We thank Cendrine Barriere Borgioni, Elena Gasparotto, and Valerie Eligert for expert technical assistance; Romain Guiet for his help for calcium imaging quantification; and Sylvain Lengacher for helpful discussions. This work was supported by Swiss National Science Foundation Grants 31003A-130821/1 and 310030B-148169/1 and by the National Centre of Competence in Research (NCCR) Synapsy and the Biaggi and Panacee Foundations (P.J.M.).
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143009
Appears in Collections:
Articles; Bioscience Program; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorYang, Jiangyanen
dc.contributor.authorRuchti, Evelyneen
dc.contributor.authorPetit, Jean Marieen
dc.contributor.authorJourdain, Pascalen
dc.contributor.authorGrenningloh, Gabrieleen
dc.contributor.authorAllaman, Igoren
dc.contributor.authorMagistretti, Pierre J.en
dc.date.accessioned2015-08-03T12:05:21Zen
dc.date.available2015-08-03T12:05:21Zen
dc.date.issued2014-07-28en
dc.identifier.issn00278424en
dc.identifier.pmid25071212en
dc.identifier.doi10.1073/pnas.1322912111en
dc.identifier.urihttp://hdl.handle.net/10754/563661en
dc.description.abstractL-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.en
dc.description.sponsorshipWe thank Cendrine Barriere Borgioni, Elena Gasparotto, and Valerie Eligert for expert technical assistance; Romain Guiet for his help for calcium imaging quantification; and Sylvain Lengacher for helpful discussions. This work was supported by Swiss National Science Foundation Grants 31003A-130821/1 and 310030B-148169/1 and by the National Centre of Competence in Research (NCCR) Synapsy and the Biaggi and Panacee Foundations (P.J.M.).en
dc.publisherProceedings of the National Academy of Sciencesen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143009en
dc.subjectAstrocyte-neuron interactionen
dc.subjectAstrocyte-neuron lactate shuttleen
dc.subjectBrain energy metabolismen
dc.subjectLearning and memoryen
dc.titleLactate promotes plasticity gene expression by potentiating NMDA signaling in neuronsen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentBioscience Programen
dc.identifier.journalProceedings of the National Academy of Sciencesen
dc.identifier.pmcidPMC4143009en
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerlanden
dc.contributor.institutionCentre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1008 Prilly/Lausanne, Switzerlanden
kaust.authorRuchti, Evelyneen
kaust.authorMagistretti, Pierre J.en

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