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    Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

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    Type
    Article
    Authors
    Yang, Jiangyan
    Ruchti, Evelyne
    Petit, Jean Marie
    Jourdain, Pascal
    Grenningloh, Gabriele
    Allaman, Igor
    Magistretti, Pierre J. cc
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2014-07-28
    Online Publication Date
    2014-07-28
    Print Publication Date
    2014-08-19
    Permanent link to this record
    http://hdl.handle.net/10754/563661
    
    Metadata
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    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.
    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.1322912111
    Sponsors
    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.).
    Publisher
    Proceedings of the National Academy of Sciences
    Journal
    Proceedings of the National Academy of Sciences
    DOI
    10.1073/pnas.1322912111
    PubMed ID
    25071212
    PubMed Central ID
    PMC4143009
    Additional Links
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143009
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.1322912111
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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