Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

Jiangyan Yang, Evelyne Ruchti, Jean Marie Petit, Pascal Jourdain, Gabriele Grenningloh, Igor Allaman, Pierre J. Magistretti

Research output: Contribution to journalArticlepeer-review

346 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)12228-12233
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume111
Issue number33
DOIs
StatePublished - Jul 28 2014

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank Cendrine Barriere Borgioni, Elena Gasparotto, and Valerie Eligert for expert technical assistance; Romain Guiet for his help for calcium imaging quantification; and Sylvain Lengacher for helpful discussions. This work was supported by Swiss National Science Foundation Grants 31003A-130821/1 and 310030B-148169/1 and by the National Centre of Competence in Research (NCCR) Synapsy and the Biaggi and Panacee Foundations (P.J.M.).

ASJC Scopus subject areas

  • General

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