Format

Send to

Choose Destination
FASEB J. 2017 Dec;31(12):5440-5452. doi: 10.1096/fj.201700221RR. Epub 2017 Aug 21.

Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration.

Author information

1
Unité Mixte de Recherche (UMR) Adaptation Biologique et Vieillissement (UMR 8256), Institut Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), INSERM, Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France.
2
Unité Signalisation et Physiopathologie Cardiovasculaire, INSERM, Université Paris-Saclay, Université Paris Sud, Châtenay-Malabry, France.
3
Equipe de Recherche Labellisée (ERL) U1164, INSERM, Université Paris-Saclay, Université Paris Sud, Châtenay-Malabry, France.
4
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
5
Unité INSERM 1237, GIP Cycéron, Centre Hospitalier Universitaire de Caen, Université Caen Normandie, Caen, France.
6
Unité Mixte de Recherche (UMR) Adaptation Biologique et Vieillissement (UMR 8256), Institut Biologie Paris Seine, Centre National de la Recherche Scientifique (CNRS), INSERM, Université Pierre et Marie Curie (UPMC), Sorbonne Universités, Paris, France; eric.duplus@upmc.fr.

Abstract

NAD+ depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD+ was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD+ to NR prompted us to probe the effects of NAD+ and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD+ reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provision of extracellular NR delays NMDA-induced axonal degeneration (AxD) much more strongly than extracellular NAD+ Moreover, the stronger effect of NR compared to NAD+ depends of axonal stress since in AxD induced by pharmacological inhibition of nicotinamide salvage, both NAD+ and NR prevent neuronal death and AxD in a manner that depends on internalization of NR. Taken together, our findings demonstrate that NR is a better neuroprotective agent than NAD+ in excitotoxicity-induced AxD and that axonal protection involves defending intracellular NAD+ homeostasis.-Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration.

KEYWORDS:

FK866; NAD+; NMDA; NR; cortical neurons

PMID:
28842432
DOI:
10.1096/fj.201700221RR
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center