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A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes

dc.rights.licenseopenen_US
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorFERNANDEZ-MONCADA, Ignacio
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorFUNDAZURI, Unai
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorLAVANCO, Gianluca
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBOLLMOHR, Nasrin
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorHACHAGUER, Pauline
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorTOR, Tommaso Dalla
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMOUNTADEM, Sarah
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorSERRAT, Roman
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBELLOCCHIO, Luigi
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCANNICH, Astrid
dc.contributor.authorNASU, Yusuke
dc.contributor.authorCAMPBELL, Robert
dc.contributor.authorDRAGO, Filippo
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBOUZIER-SORE, Anne-Karine
dc.contributor.authorPELLERIN, Luc
dc.contributor.authorBOLAÑOS, Juan
dc.contributor.authorBONVENTO, Gilles
dc.contributor.authorFELIPE BARROS, L.
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorOLIET, Stephane
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorPANATIER, Aude
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMARSICANO, Giovanni
dc.date.accessioned2023-11-28T16:14:50Z
dc.date.available2023-11-28T16:14:50Z
dc.date.issued2023-03-01
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/186205
dc.description.abstractEnABSTRACT Control of brain energy metabolism and regulation of synaptic activity through gliotransmission are two important ways, through which astrocytes contribute to mental functions. However, the potential functional and molecular links between these two astrocyte-dependent processes have been scantly explored so far. Here we show that a lactate-dependent shift of glycolysis underlies the production of the gliotransmitter D-serine by acute activation of astrocyte type-1 cannabinoid (CB1) receptors, thereby gating synaptic and cognitive processes. Acute cannabinoid application causes a CB1 receptor-dependent rapid and reversible increase of lactate production and release in primary astrocyte cultures. As shown before, mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) were impaired in a novel object recognition (NOR) task. Notably, this phenotype was rescued not only by the gliotransmitter D-serine, but also by its precursor L-serine. Surprisingly, the administration of lactate also reverted the memory impairment of GFAP-CB1-KO mice. This rescue effect was abolished by in vivo blockade of the astrocyte-specific phosphorylated pathway (PP), which diverts glycolysis towards L-serine synthesis, suggesting that lactate itself might promote the accumulation of this amino acid. Consistent with this idea, lactate increased the co-agonist occupancy of CA1 post-synaptic hippocampal NMDA receptors in a PP-dependent manner. By establishing a mechanistic link between lactate, serine availability, synaptic activity and behavior, these results reveal an unforeseen functional connection between energy metabolism and gliotransmission to control cognitive processes.
dc.description.sponsorshipDéveloppement d'une infrastructure française distribuée coordonnéeen_US
dc.description.sponsorshipRecepteurs aux cannabinoides dans le codage visuel corticalen_US
dc.description.sponsorshipRôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité. - ANR-18-CE14-0029en_US
dc.description.sponsorshipInvolvement of the insula in the Autism neurodevelopmental disorderen_US
dc.description.sponsorshipRôle des différents substrats énergétiques pour l'activité cérébrale - ANR-21-CE44-0023en_US
dc.description.sponsorshipRôle et Physiologie Cellulaire de Nouveaux Récepteurs Glycine Excitateurs dans le Cerveau Antérieuren_US
dc.description.sponsorshipLes exosomes, un nouveau mode de communication entre les astrocytes et les neurones avec de possibles implications dans la maladie d'Alzheimeren_US
dc.description.sponsorshipRole du recepteur CB1 mitocondriel du tissue adipeux dans la regulation de la balance energetique - ANR-19-CE14-0039en_US
dc.description.sponsorshipInitiative d'excellence de l'Université de Bordeauxen_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enCB1 receptor
dc.subject.enAstrocytes
dc.subject.enEnergy metabolism
dc.subject.enLactate
dc.subject.enSerine
dc.subject.enNMDAR
dc.subject.enGliotransmission
dc.subject.enNeurotransmission
dc.title.enA lactate-dependent shift of glycolysis mediates synaptic and cognitive processes
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1101/2023.03.15.532748en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
bordeaux.journalBioRxiven_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamRelations glie-neuroneen_US
bordeaux.teamEndocannabinoïdes et Neuroadaptationen_US
bordeaux.identifier.funderIDHorizon 2020en_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.identifier.funderIDFONDATION ALZHEIMERen_US
bordeaux.identifier.funderIDAgencia Estatal de Investigaciónen_US
bordeaux.import.sourcehal
hal.identifierhal-04310383
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccCC BY-NC-NDen_US
bordeaux.subtypePrepublication/Preprinten_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=BioRxiv&rft.date=2023-03-01&rft.au=FERNANDEZ-MONCADA,%20Ignacio&FUNDAZURI,%20Unai&LAVANCO,%20Gianluca&BOLLMOHR,%20Nasrin&HACHAGUER,%20Pauline&rft.genre=preprint


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