Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection
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| 024 | 7 | 0 | |a 10.1038/s41598-018-31534-y |2 doi |
| 035 | |a (SERVAL)BIB_D8205C7F651E | ||
| 091 | |a 30194439 |b pmid | ||
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| 245 | 0 | 0 | |a Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection |h [Elektronische Daten] |c [P. Jourdain, K. Rothenfusser, C. Ben-Adiba, I. Allaman, P. Marquet, P.J. Magistretti] |
| 520 | 3 | |a 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. | |
| 700 | 1 | |a Jourdain |D P. |4 aut | |
| 700 | 1 | |a Rothenfusser |D K. |4 aut | |
| 700 | 1 | |a Ben-Adiba |D C. |4 aut | |
| 700 | 1 | |a Allaman |D I. |4 aut | |
| 700 | 1 | |a Marquet |D P. |4 aut | |
| 700 | 1 | |a Magistretti |D P.J. |4 aut | |
| 773 | 0 | |t Scientific reports |g 8/1(2018-09-07), 13472 |q 8:1<13472 |1 2018 |2 8 | |
| 908 | |D 1 |a article |2 serval | ||
| 950 | |B SERVAL |P 700 |E 1- |a Jourdain |D P. |4 aut | ||
| 950 | |B SERVAL |P 700 |E 1- |a Rothenfusser |D K. |4 aut | ||
| 950 | |B SERVAL |P 700 |E 1- |a Ben-Adiba |D C. |4 aut | ||
| 950 | |B SERVAL |P 700 |E 1- |a Allaman |D I. |4 aut | ||
| 950 | |B SERVAL |P 700 |E 1- |a Marquet |D P. |4 aut | ||
| 950 | |B SERVAL |P 700 |E 1- |a Magistretti |D P.J. |4 aut | ||
| 950 | |B SERVAL |P 773 |E 0- |t Scientific reports |g 8/1(2018-09-07), 13472 |q 8:1<13472 |1 2018 |2 8 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B SERVAL |F SERVAL |b SERVAL |j article | ||