Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection.

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Version: Final published version
Serval ID
serval:BIB_D8205C7F651E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection.
Journal
Scientific reports
Author(s)
Jourdain P., Rothenfusser K., Ben-Adiba C., Allaman I., Marquet P., Magistretti P.J.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
07/09/2018
Peer-reviewed
Oui
Volume
8
Number
1
Pages
13472
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
L-Lactate is a positive modulator of NMDAR-mediated signaling resulting in plasticity gene induction and memory consolidation. However, L-Lactate is also able to protect neurons against excito-toxic NMDAR activity, an indication of a mitigating action of L-Lactate on NMDA signaling. In this study, we provide experimental evidence that resolves this apparent paradox. Transient co-application of glutamate/glycine (1 μM/100 μM; 2 min) in primary cultures of mouse cortical neurons triggers a NMDA-dependent Ca <sup>2+</sup> signal positively modulated by L-Lactate (10 mM) or DTT (1 mM) but decreased by Pyruvate (10 mM). This L-Lactate and DTT-induced potentiation is blocked by Ifenprodil (2 μM), a specific blocker of NMDARs containing NR2B sub-units. In contrast, co-application of glutamate/glycine (1 mM/100 μM; 2 min) elicits a NMDAR-dependent excitotoxic death in 49% of neurons. L-Lactate and Pyruvate significantly reduce this rate of cell death processes (respectively to 23% and 9%) while DTT has no effect (54% of neuronal death). This L-Lactate-induced neuroprotection is blocked by carbenoxolone and glibenclamide, respectively blockers of pannexins and K <sub>ATP</sub> . In conclusion, our results show that L-Lactate is involved in two distinct and independent pathways defined as NMDAR-mediated potentiation pathway (or NADH pathway) and a neuroprotective pathway (or Pyruvate/ATP pathway), the prevalence of each one depending on the strength of the glutamatergic stimulus.
Pubmed
Web of science
Open Access
Yes
Create date
20/09/2018 8:46
Last modification date
16/12/2020 6:26
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