Altschuler Richard A, Fairfield Damon, Cho Younsook, Leonova Elena, Benjamin Ivor J, Miller Josef M, Lomax Margaret I
Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109-0506, USA.
Audiol Neurootol. 2002 May-Jun;7(3):152-6. doi: 10.1159/000058301.
Noise overstimulation will induce or influence intracellular molecular pathways in the cochlea. One of these is the 'classical' stress response pathway involving heat shock proteins. Hsp70 is induced in the cochlea by a wide variety of stresses including noise, hyperthermia and ototoxic drugs. When a stress that induces Hsp70 is applied to the cochlea, there is protection from a subsequent noise that would normally cause a permanent hearing loss. An upstream regulator of heat shock protein transcription, heat shock factor 1, is expressed in the cochlea and activated by stress. Mice lacking this heat shock factor have reduced recovery from noise-induced hearing loss. The same noise exposure that induces Hsp70 also increases the level of glial cell line-derived neurotrophic factor in the cochlea. Moreover, when this neurotrophic factor is applied into the perilymph of scala tympani prior to a noise exposure there is a significant reduction in hair cell loss and hearing loss. With the potential for activation of multiple pathways in the response to noise, gene microarrays can be useful to examine global gene expression. Initial studies examined differential gene expression immediately following a mild noise exposure (from which there is complete recovery) versus an intense noise (giving profound permanent deafness). Differential expression of several immediate early genes was found following the intense but not the mild noise exposure.
噪声过度刺激会诱导或影响耳蜗内的细胞内分子通路。其中之一是涉及热休克蛋白的“经典”应激反应通路。包括噪声、高温和耳毒性药物在内的多种应激可诱导耳蜗中的热休克蛋白70（Hsp70）。当将诱导Hsp70的应激施加于耳蜗时，可保护其免受随后通常会导致永久性听力损失的噪声影响。热休克蛋白转录的上游调节因子热休克因子1在耳蜗中表达并被应激激活。缺乏这种热休克因子的小鼠从噪声诱导的听力损失中的恢复能力降低。诱导Hsp70的相同噪声暴露也会增加耳蜗中胶质细胞源性神经营养因子的水平。此外，在噪声暴露之前将这种神经营养因子注入鼓阶外淋巴中，可显著减少毛细胞损失和听力损失。鉴于噪声反应中存在激活多种通路的可能性，基因微阵列可用于检测整体基因表达。初步研究检查了轻度噪声暴露（可完全恢复）后与重度噪声暴露（导致严重永久性耳聋）后立即出现的基因差异表达。在重度而非轻度噪声暴露后发现了几种即刻早期基因的差异表达。
