caa a22 4500 528788388 CHVBK 20190303132846.0 cr unu---uuuuu 180924e20180907xx s 000 0 eng 10.1038/s41598-018-31534-y doi (SERVAL)BIB_D8205C7F651E 30194439 pmid 000444024100007 isiid Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection [Elektronische Daten] [P. Jourdain, K. Rothenfusser, C. Ben-Adiba, I. Allaman, P. Marquet, P.J. Magistretti] 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 &lt;sup&gt;2+&lt;/sup&gt; 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 &lt;sub&gt;ATP&lt;/sub&gt; . 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. Jourdain P. aut Rothenfusser K. aut Ben-Adiba C. aut Allaman I. aut Marquet P. aut Magistretti P.J. aut Scientific reports 8/1(2018-09-07), 13472 8:1<13472 2018 8 1 article serval SERVAL 700 1- Jourdain P. aut SERVAL 700 1- Rothenfusser K. aut SERVAL 700 1- Ben-Adiba C. aut SERVAL 700 1- Allaman I. aut SERVAL 700 1- Marquet P. aut SERVAL 700 1- Magistretti P.J. aut SERVAL 773 0- Scientific reports 8/1(2018-09-07), 13472 8:1<13472 2018 8 BK010053 XK010053 XK010000 SERVAL SERVAL SERVAL article