Journal Article

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

Bouzier-Sore, Anne-Karine, ANR-21-NEU2-0001,CANSHANK,Involvement of the insula in the Autism neurodevelopmental disorder, University of Tokyo [Tokyo] = Tōkyō teikoku daigaku (UTokyo), Bellocchio, Luigi, Dalla Tor, Tommaso, Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313] (IRMETIST [Poitiers]) ; Université de Poitiers = University of Poitiers (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et Neurobiologie intégrée (NutriNeuro) ; Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hachaguer, Pauline, Università degli studi di Catania = University of Catania (Unict), ANR-23-CE16-0022,CaMeLS,Récepteurs CB1, bioénergétique et mémoire : une nouvelle interaction métabolique entre le lactate et la sérine, Serrat, Roman, Centre hospitalier universitaire de Poitiers = Poitiers Univers

2024

Overview

Astrocytes control brain activity via both metabolic processes and gliotransmission, but the physiological links between these functions are scantly known. Here we show that endogenous activation of astrocyte type-1 cannabinoid (CB1) receptors determines a shift of glycolysis towards the lactate-dependent production of D-serine, thereby gating synaptic and cognitive functions in male mice. Mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) are impaired in novel object recognition (NOR) memory. This phenotype is rescued by the gliotransmitter D-serine, by its precursor L-serine, and also by lactate and 3,5-DHBA, an agonist of the lactate receptor HCAR1. Such lactate-dependent effect is abolished when the astrocyte-specific phosphorylated-pathway (PP), which diverts glycolysis towards L-serine synthesis, is blocked. Consistently, lactate and 3,5-DHBA promoted the co-agonist binding site occupancy of CA1 post-synaptic NMDA receptors in hippocampal slices in a PP-dependent manner. Thus, a tight cross-talk between astrocytic energy metabolism and gliotransmission determines synaptic and cognitive processes.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 13 / 13/106 / 14/10 / 14/33 / 14/63 / 42/41 / 631/378/1595/2638 / 631/378/2596/1308 / 64/60 / 9/30 / Agonists / Animals / Astrocytes / Astrocytes - metabolism / Binding sites / Brain slice preparation / Cannabinoid CB1 receptors / Cannabinoids / Channel gating / Cognition / Cognition & reasoning / Cognition - physiology / Cognitive ability / D-Serine / Energy metabolism / Glial fibrillary acidic protein / Glutamic acid receptors (ionotropic) / Glycolysis / Hippocampus / Hippocampus - metabolism / Humanities and Social Sciences / L-Serine / Lactic acid / Lactic Acid - metabolism / Life Sciences / Male / Males / Metabolic rate / Metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / multidisciplinary / N-Methyl-D-aspartic acid receptors / Object recognition / Pattern recognition / Phenotypes / Receptors / Receptors, G-Protein-Coupled - genetics / Receptors, G-Protein-Coupled - metabolism / Receptors, N-Methyl-D-Aspartate - genetics / Receptors, N-Methyl-D-Aspartate - metabolism / Science / Science (multidisciplinary) / Serine - metabolism / Synapses - metabolism
• ISBN: 0012972216000