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dc.contributor.authorYang, Jiangyan
dc.contributor.authorRuchti, Evelyne
dc.contributor.authorPetit, Jean Marie
dc.contributor.authorJourdain, Pascal
dc.contributor.authorGrenningloh, Gabriele
dc.contributor.authorAllaman, Igor
dc.contributor.authorMagistretti, Pierre J.
dc.date.accessioned2015-08-03T12:05:21Z
dc.date.available2015-08-03T12:05:21Z
dc.date.issued2014-07-28
dc.identifier.issn00278424
dc.identifier.pmid25071212
dc.identifier.doi10.1073/pnas.1322912111
dc.identifier.urihttp://hdl.handle.net/10754/563661
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.
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.).
dc.publisherProceedings of the National Academy of Sciences
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143009
dc.subjectAstrocyte-neuron interaction
dc.subjectAstrocyte-neuron lactate shuttle
dc.subjectBrain energy metabolism
dc.subjectLearning and memory
dc.titleLactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalProceedings of the National Academy of Sciences
dc.identifier.pmcidPMC4143009
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
dc.contributor.institutionCentre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1008 Prilly/Lausanne, Switzerland
kaust.personRuchti, Evelyne
kaust.personMagistretti, Pierre J.
dc.date.published-online2014-07-28
dc.date.published-print2014-08-19


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