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7,8,3 '-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo

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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 [4]Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
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关键词: Spiral ganglion neurons 7 8 3 '-Trihydroxyflavone Neuronal degeneration BDNF TrkB receptor Gjb2 deletion Cochlea Neurotrophic factors Small molecule Mouse model

摘要:
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.

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出版当年[2011]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学 4 区 生物物理
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出版当年[2010]版:
Q3 BIOPHYSICS Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

影响因子: 最新[2023版] 最新五年平均 出版当年[2010版] 出版当年五年平均 出版前一年[2009版] 出版后一年[2011版]

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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
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