title: Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons.
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.
authors: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;
authors: Jiangyan
authors: J
authors: Yang
authors: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; andCentre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), Site de Cery, CH-1008 Prilly/Lausanne, Switzerland.
authors: Evelyne
authors: E
authors: Ruchti
authors: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;Centre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), Site de Cery, CH-1008 Prilly/Lausanne, Switzerland.
authors: Jean-Marie
authors: JM
authors: Petit
authors: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;Centre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), Site de Cery, CH-1008 Prilly/Lausanne, Switzerland.
authors: Pascal
authors: P
authors: Jourdain
authors: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland;
authors: Gabriele
authors: G
authors: Grenningloh
authors: Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; igor.allaman@epfl.ch pierre.magistretti@kaust.edu.sa.
authors: Igor
authors: http://orcid.org/0000-0002-7525-0536
authors: I
authors: Allaman
authors: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia; andCentre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois (CHUV), Site de Cery, CH-1008 Prilly/Lausanne, SwitzerlandLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; igor.allaman@epfl.ch pierre.magistretti@kaust.edu.sa.
authors: Pierre J
authors: PJ
authors: Magistretti
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D019344:Lactic Acid / Q000494:pharmacology*; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019344:Lactic Acid; D016202:N-Methylaspartate; D002118:Calcium
keywords: astrocyte–neuron interaction; astrocyte–neuron lactate shuttle; brain energy metabolism; learning and memory