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Neuroscience. 2016 Mar 1;316:311-20. doi: 10.1016/j.neuroscience.2015.12.050. Epub 2015 Dec 31.

Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice.

Author information

1
Department of Otorhinolaryngology-Head & Neck Surgery, Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an 710014, Shaanxi, PR China; Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
2
Department of Otorhinolaryngology-Head & Neck Surgery, Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an 710014, Shaanxi, PR China.
3
Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
4
Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China.
5
Department of Otorhinolaryngology-Head & Neck Surgery, Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an 710014, Shaanxi, PR China; Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Transformative Otology and Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China. Electronic address: qyz@case.edu.

Abstract

Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cadherin23 (Cdh23) gene, Cdh23(erl/erl), was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23(erl/erl) mice (erl mice), this study investigated TUDCA's otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12.

KEYWORDS:

Cdh23; apoptosis; hearing loss; otoprotection; tauroursodeoxycholic acid (TUDCA)

PMID:
26748055
PMCID:
PMC4724520
[Available on 2017-03-01]
DOI:
10.1016/j.neuroscience.2015.12.050
[Indexed for MEDLINE]
Free PMC Article

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