Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss.
Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss.
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DOI：
10.1016/j.heares.2015.02.009
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发表时间：
2015-12
期刊：
影响因子：
2.8
通讯作者：
Liberman MC
中科院分区：
文献类型：
--
作者：
Kujawa SG;Liberman MC
感音神经性听力损失（SNHL）的经典观点是“主要”目标是毛细胞，耳蜗神经损失是毛细胞变性的“次要”。我们最近在小鼠和豚鼠身上的研究对这种观点提出了挑战。在噪声引起的听力损失中，暴露仅引起可逆的阈值偏移（并且没有毛细胞损失），但会导致>50%的耳蜗神经/毛细胞突触的永久性损失。类似地，在与年龄相关的听力损失中，耳蜗突触的退化先于毛细胞损失和阈值升高。这种原发性神经变性由于三个原因而一直被隐藏：1）螺旋神经节细胞，通常在SNHL研究中评估的耳蜗神经元件，尽管失去了与毛细胞的突触连接，但仍存活多年，2）耳蜗神经纤维的突触末端是无髓鞘的，并且在光学显微镜下难以看到，以及3）变性对具有高阈值的耳蜗神经纤维是选择性的。虽然不需要在安静的阈值检测（例如阈值测听或听觉脑干反应阈值），这些高阈值纤维是在嘈杂的环境中听力的关键。我们的研究表明，1）原发性神经变性是SNHL中感知障碍的重要因素，2）在毛细胞存活的情况下，神经营养因子治疗可以引起螺旋神经节神经元的轴突生长并重建其外周突触。
The classic view of sensorineural hearing loss (SNHL) is that the “primary” targets are hair cells, and that cochlear-nerve loss is “secondary” to hair cell degeneration. Our recent work in mouse and guinea pig has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear-nerve / hair-cell synapses. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained hidden for three reasons: 1) the spiral ganglion cells, the cochlear neural elements commonly assessed in studies of SNHL, survive for years despite loss of synaptic connection with hair cells, 2) the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to see in the light microscope, and 3) the degeneration is selective for cochlear-nerve fibers with high thresholds. Although not required for threshold detection in quiet (e.g. threshold audiometry or auditory brainstem response threshold), these high-threshold fibers are critical for hearing in noisy environments. Our research suggests that 1) primary neural degeneration is an important contributor to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons and re-establishment of their peripheral synapses.