Format

Send to

Choose Destination
Cell Metab. 2014 Dec 2;20(6):1059-68. doi: 10.1016/j.cmet.2014.11.003.

Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss.

Author information

1
Department of Otolaryngology-Head and Neck Surgery, Weill Medical College, Cornell University, New York, NY 10065, USA. Electronic address: kevin_d_brown@med.unc.edu.
2
Department of Otolaryngology-Head and Neck Surgery, Weill Medical College, Cornell University, New York, NY 10065, USA.
3
Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94941, USA.
4
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA.
5
Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94941, USA. Electronic address: eric.verdin@gladstone.ucsf.edu.
6
Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA. Electronic address: srj2003@med.cornell.edu.

Abstract

Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum instability. Here, we describe a strategy to increase cochlear NAD(+) levels in mice by administering nicotinamide riboside (NR), a recently described NAD(+) precursor. We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD(+) biosynthetic enzymes. These findings reveal that administration of NR activates a NAD(+)-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.

Comment in

PMID:
25470550
PMCID:
PMC4940130
DOI:
10.1016/j.cmet.2014.11.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center