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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
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Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
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Journal Article
Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
2014
Overview
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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Brain
/ Calcium
/ cortex
/ energy
/ Gene Expression - drug effects
/ genes
/ Lactates
/ Memory
/ Mice
/ N-Methylaspartate - metabolism
/ Neuronal Plasticity - genetics
/ Neurons
/ Rodents
