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

Détails

Ressource 1Télécharger: 30194439.pdf (4338.00 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_D8205C7F651E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection.
Périodique
Scientific reports
Auteur(s)
Jourdain P., Rothenfusser K., Ben-Adiba C., Allaman I., Marquet P., Magistretti P.J.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
07/09/2018
Peer-reviewed
Oui
Volume
8
Numéro
1
Pages
13472
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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
Oui
Création de la notice
20/09/2018 8:46
Dernière modification de la notice
20/08/2019 15:57
Données d'usage