AAV-mediated NT-3 overexpression protects cochleae against noise-induced synaptopathy.

AAV-mediated NT-3 overexpression protects cochleae against noise-induced synaptopathy.
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DOI:
10.1038/s41434-018-0012-0
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发表时间:
2018-07
期刊:
影响因子:
5.1
通讯作者:
Wang J
Wang J
中科院分区:
医学3区
文献类型:
--
作者:
Chen H;Xing Y;Xia L;Chen Z;Yin S;Wang J

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哺乳动物耳蜗内毛细胞与Ⅰ型螺旋神经节神经元之间的突触是噪声损伤的敏感结构。由于这个突触提供了从耳蜗到听觉大脑的主要信息通路,因此保持其完整性非常重要。神经营养素-3(NT-3)在突触的发育和功能维持中起重要作用。外源性NT-3的应用,或在转基因动物模型中过表达该基因,已经显示出保护该突触免受噪声诱导的损伤的价值。在本研究中,NT-3过表达诱导耳蜗基因转染噪声暴露前,通过使用腺相关病毒(AAV)载体。我们发现,这种过表达提供了一种显着的突触保护,以防止噪音暴露对突触造成大规模损伤,这可能是由于它促进了突触在初始损伤后的修复。
The synapse between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) has been identified as a sensitive structure to noise-induced damage in the mammalian cochlea. Since this synapse provides the major information pathway from the cochlea to the auditory brain, it is important to maintain its integrity. Neurotrophin-3 (NT-3) has been known to play an important role in the development and the functional maintenance of this synapse. Application of exogenous NT-3, or overexpression of this gene in a transgenic animal model, have shown the value to protect this synapse from noise-induced damage. In the present study, NT-3 overexpression was induced by cochlear gene transfection before noise exposure via the use of an adeno-associated viral (AAV) vector. We found that such an overexpression provided a significant synaptic protection against a noise exposure that caused massive damage to the synapses, likely due to it promoting the repair of the synapse after the initial damage.
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