Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
Type
ArticleAuthors
Yang, JiangyanRuchti, Evelyne
Petit, Jean Marie
Jourdain, Pascal
Grenningloh, Gabriele
Allaman, Igor
Magistretti, Pierre J.

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Date
2014-07-28Online Publication Date
2014-07-28Print Publication Date
2014-08-19Permanent link to this record
http://hdl.handle.net/10754/563661
Metadata
Show full item recordAbstract
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.Citation
Yang, J., Ruchti, E., Petit, J.-M., Jourdain, P., Grenningloh, G., Allaman, I., & Magistretti, P. J. (2014). Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proceedings of the National Academy of Sciences, 111(33), 12228–12233. doi:10.1073/pnas.1322912111Sponsors
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.).PubMed ID
25071212PubMed Central ID
PMC4143009Additional Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143009ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1322912111
Scopus Count
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