Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
2014
Yang, Jiangyan | Ruchti, Evelyne | Petit, Jean-Marie | Jourdain, Pascal | Grenningloh, Gabriele | Allaman, Igor | Magistretti, Pierre J.
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.
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