Food and Behaviour Research

Donate Log In

Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

Brown KD, Maqsood S, Huang J-Y, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR (2014) Cell Metabolism 20 (6) 1059–1068 

Web URL: Read more on the Journal website here

Abstract:

Highlights 

  • The NAD+ precursor NR prevents noise-induced hearing loss
  • NR can be administered after acoustic trauma to prevent hearing loss
  • Prevention of noise-induced hearing loss by NAD+ and NR is dependent upon SIRT3
  • NAD+ and NR prevent noise-induced neurite retraction in the cochlea

Summary

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 SIRT3deletion 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.