Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss Academic Article uri icon

Overview

MeSH Major

  • Hearing Loss, Noise-Induced
  • NAD
  • Niacinamide
  • Sirtuin 3

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.

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4940130

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2014.11.003

PubMed ID

  • 25470550

Additional Document Info

start page

  • 1059

end page

  • 68

volume

  • 20

number

  • 6