Otoprotective effects of mouse nerve growth factor in DBA/2J mice with early-onset progressive hearing loss.

Otoprotective effects of mouse nerve growth factor in DBA/2J mice with early-onset progressive hearing loss.
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小鼠神经生长因子对早发进行性听力损失 DBA/2J 小鼠的耳保护作用

DOI:
10.1002/jnr.24056
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发表时间:
2017-10
影响因子:
4.2
通讯作者:
Zheng Q
Zheng Q
中科院分区:
医学3区
文献类型:
--
作者:
Wang Q;Zhao H;Zheng T;Wang W;Zhang X;Wang A;Li B;Wang Y;Zheng Q

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DBA/2 J是一种广泛用于听力研究的近交系小鼠品系,因为它表现出以早发性进行性听力损失(ePHL)为特征的进行性毛细胞损失和螺旋神经节神经元(SGN)变性。小鼠神经生长因子(mNGF)作为一种常见的外源性神经生长因子,因其促进神经元存活和生长的能力而被广泛研究。为了确定mNGF是否可以改善DBA/2 J小鼠中的进行性听力损失(PHL),从出生后第1至第9周通过每天肌肉注射向任一性别的DBA/2 J小鼠给予生理盐水或mNGF。在5、7和9周龄时,与溶剂组相比,mNGF组经历了听觉诱发的脑干反应(ABR)阈值降低和畸变产物耳声发射(DPOAE)振幅增加,毛细胞丢失的预防和SGN凋亡的抑制。采用Real-time PCR、Western Blot和免疫组化方法检测mNGF对小鼠耳蜗巴克/Bax和Caspase基因和蛋白表达的影响。提示Bak-dependent线粒体凋亡途径可能参与了mNGF对DBA/2 J小鼠进行性听力损失的耳保护机制。本研究结果表明,mNGF可作为DBA/2 J小鼠PHL早期干预的耳保护剂,具有重要的临床应用价值。mNGF可抑制螺旋神经节细胞凋亡,防止血管纹变性,保护毛细胞。最终,mNGF保护DBA/2 J小鼠的年龄相关性听力损失。
DBA/2J is an inbred mouse strain widely used in hearing research, as it displays progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL). Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth. At 5, 7, and 9 weeks of age, in comparison with vehicle groups, mNGF groups experienced decreased auditory-evoked brainstem response (ABR) thresholds and increased distortion product otoacoustic emission (DPOAE) amplitudes, the prevention of hair cell loss, and the inhibition of apoptosis of SGNs. Downregulation of Bak/Bax and Caspase genes and proteins in cochleae of mice receiving the mNGF treatment was detected by Real-time PCR, Western Blot and Immunohistochemistry. This suggests that the Bak-dependent mitochondrial apoptosis pathway may be involved in the otoprotective mechanism of mNGF in progressive hearing loss of DBA/2J mice. Our results demonstrate that mNGF can act as an otoprotectant in the DBA/2J mice for the early intervention of PHL and, thus, could become of great value in clinical applications. mNGF can inhibit apoptosis of the spiral ganglion cells, prevent degeneration of stria vascularis and protect the hair cells. Ultimately, mNGF protect the age related hearing loss in the DBA/2J mice.
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