Histone deacetylase inhibition protects hearing against acute ototoxicity by activating the Nf-B pathway.

Auditory hair cells have repeatedly been shown to be susceptible to ototoxicity from a multitude of drugs including aminoglycoside antibiotics. Here, we found that systemic HDAC inhibition using suberoylanilide hydroxamic acid (SAHA) on adult mice offers almost complete protection against hair cell loss and hearing threshold shifts from acute ototoxic insult from kanamycin potentiated with furosemide. We also found that the apparent lack of hair cell loss was completely independent of spontaneous or facilitated (ectopic induction) hair cell regeneration.

Epigenetic alterations by NuRD and PRC2 in the neonatal mouse cochlea.

Mammalian cochlear supporting cells remain quiescent at postnatal ages and age-dependent changes in supporting cell proliferative capacity are evident. Ectopic Atoh1 expression in neonatal supporting cells converts only a small percentage of these cells into hair cell-like cells. Despite tremendous potential for therapeutics, cellular reprogramming in the mammalian inner ear remains a slow inefficient process that requires weeks, with most cells failing to reprogram.