Most sensorineural hearing loss cases occur as a result of hair cell loss, which results in secondary degeneration of spiral ganglion neurons (SGNs). Substantial loss of SGNs reduces the benefit of cochlear implants, which rely on SGNs for transmitting signals to the central auditory centers. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) play essential roles in cochlear development and are required for SGN survival. Here we report that 7,8,3'-trihydroxyflavone (7,8,3'-THF), which is a small molecule agonist of tyrosine receptor kinase B (TrkB), promoted SGN survival with high potency both in vitro and in vivo. The compound protected the SGNs in a TrkB-dependent manner, as its effects on SGNs disappeared when the TrkB was blocked. Application of 7,8,3'-THF in the bulla of conditional connexin26 (cCx26)-null mice dramatically rescued SGNs in the applied ear compared to untreated control cochlea in the same animal. Our findings suggest that 7,8,3'-THF is a promising therapeutic agent protecting the SGNs from degeneration both in vitro and in vivo. (c) 2012 Elsevier Inc. All rights reserved.
基金:
National Institute on Deafness and other Communication Disorders (NIDCD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Deafness & Other Communication Disorders (NIDCD) [R01DC010204, RO1 DC006483, 4R33DC010476]; [RO1 DC010204]; NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Deafness & Other Communication Disorders (NIDCD) [R01DC006483, R33DC010476, R01DC010204] Funding Source: NIH RePORTER
第一作者机构:[1]Capital Med Univ, Being Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China[2]Emory Univ, Sch Med, Dept Otolaryngol, Atlanta, GA 30322 USA
通讯作者:
通讯机构:[1]Capital Med Univ, Being Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China[2]Emory Univ, Sch Med, Dept Otolaryngol, Atlanta, GA 30322 USA[3]Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA[*1]Emory Univ, Sch Med, Dept Otolaryngol & Cell Biol, Whitehead Bldg,Room 543, Atlanta, GA 30322 USA
推荐引用方式(GB/T 7714):
Yu Qing,Chang Qing,Liu Xia,et al.7,8,3 '-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2012,422(3):387-392.doi:10.1016/j.bbrc.2012.04.154.
APA:
Yu, Qing,Chang, Qing,Liu, Xia,Gong, Shusheng,Ye, Keqiang&Lin, Xi.(2012).7,8,3 '-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,422,(3)
MLA:
Yu, Qing,et al."7,8,3 '-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 422..3(2012):387-392