Cellular signaling protective against noise-induced hearing loss – A role for novel intrinsic cochlear signaling involving corticotropin-releasing factor?
Cellular signaling protective against noise-induced hearing loss – A role for novel intrinsic cochlear signaling involving corticotropin-releasing factor?
复制标题
细胞信号传导可预防噪音引起的听力损失 – 涉及促肾上腺皮质激素释放因子的新型内在耳蜗信号传导的作用？
DOI：
10.1016/j.bcp.2015.06.011
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发表时间：
2015
影响因子：
5.8
通讯作者：
Vetter,DouglasE
中科院分区：
文献类型：
--
作者：
Vetter,DouglasE
听力损失困扰着世界上大约15%的人口，并且跨越了所有的社会经济界限。虽然在理解综合征性和非综合征性听力损失的遗传成分方面已经取得了长足的进步，但对噪声性听力损失(NIHL)的潜在机制的了解却缓慢得多。NIHL不仅仅是老年人丧失听力的一种机制。值得注意的是，NIHL的发病率正在增加，现在涉及的人群越来越年轻。这可能预示着未来听力损失的发生率会增加。目前的研究表明，即使是短期暴露在嘈杂的声音中，导致以前被认为是暂时性的听力损失，实际上也会导致特定数量的听神经纤维几乎立即和永久性地丧失。此外，反复暴露在强烈的声音中可能会加速与年龄相关的听力损失。虽然NIHL是一个重要的医学问题，但到目前为止，很少有化合物提供显著的保护，认为需要确定新的靶点。在这篇评论中，我们将探索在耳蜗中发生的细胞信号过程，据信与听力损失的保护有关，并突出新的数据提示，新的信号可能是以前没有被认为发生在耳蜗中的，这可能是对听力的保护。这包括最近描述的局部下丘脑-垂体-肾上腺轴(HPA)样信号系统，完全包含在耳蜗处。这个系统可能代表了一个局部的细胞应激反应系统，其基础是类似于全身性HPA轴的应激激素释放。这一发现可能会为新的药物疗法带来希望，这种药物可以直接输送到耳蜗处，绕过全身副作用。
Hearing loss afflicts approximately 15% of the world's population, and crosses all socioeconomic boundaries. While great strides have been made in understanding the genetic components of syndromic and non-syndromic hearing loss, understanding of the mechanisms underlying noise-induced hearing loss (NIHL) have come much more slowly. NIHL is not simply a mechanism by which older individuals loose their hearing. Significantly, the incidence of NIHL is increasing, and is now involving ever younger populations. This may predict future increased occurrences of hearing loss. Current research has shown that even short-term exposures to loud sounds generating what was previously considered temporary hearing loss, actually produces an almost immediate and permanent loss of specific populations of auditory nerve fibers. Additionally, recurrent exposures to intense sound may hasten age-related hearing loss. While NIHL is a significant medical concern, to date, few compounds have delivered significant protection, arguing that new targets need to be identified. In this commentary, we will explore cellular signaling processes taking place in the cochlea believed to be involved in protection against hearing loss, and highlight new data suggestive of novel signaling not previously recognized as occurring in the cochlea, that is perhaps protective of hearing. This includes a recently described local hypothalamic–pituitary–adrenal axis (HPA)-like signaling system fully contained in the cochlea. This system may represent a local cellular stress–response system based on stress hormone release similar to the systemic HPA axis. Its discovery may hold hope for new drug therapies that can be delivered directly to the cochlea, circumventing systemic side effects.