Association between histone deacetylases and the loss of cochlear hair cells: Role of the former in noise-induced hearing loss.

Abstract

Noise-induced hearing loss (NIHL) is one of the most frequent disabilities in industrialized countries. It has been demonstrated that hair cell loss in the auditory end organ may account for the majority of ear pathological conditions. Previous studies have indicated that histone deacetylases (HDACs) play an important role in neurodegenerative diseases, including hearing impairment, in older persons. Thus, we hypothesized that the inhibition of HDACs would prevent hair cell loss and, consequently, NIHL. In the present study, a CBA/J mouse model of NIHL was established. Following an injection with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), the expression levels of HDAC1, HDAC4 and acetyl-histone H3 (Lys9) (H3-AcK9) were measured. The number of hair cells was quantified and their morphology was observed. The results revealed that 1 h following exposure to 110 dB SPL broadband noise, there was a significant increase in HDAC1 and HDAC4 expression, and a marked decrease in the H3-AcK9 protein levels, as shown by western blot analysis. Pre-treatment with SAHA significantly inhibited these effects. Two weeks following exposure to noise, the mice exhibited significant hearing impairment and an obvious loss in the number of outer hair cells. An abnormal cell morphology with cilia damage was also observed. Pre-treatment with SAHA markedly attenuated these noise-induced effects. Taken together, the findings of our study suggest that HDAC expression is associated with outer hair cell function and plays a significant role in NIHL. Our data indicate that SAHA may be a potential therapeutic agent for the prevention of NIHL.