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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Brown KD,Maqsood S,Huang JY,Pan Y,Harkcom W,Li W,Sauve A,Verdin E,Jaffrey SRdoi
10.1016/j.cmet.2014.11.003subject
Has Abstractpub_date
2014-12-02 00:00:00pages
1059-68issue
6eissn
1550-4131issn
1932-7420pii
S1550-4131(14)00500-2journal_volume
20pub_type
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