The Role of Glia in the Peripheral and Central Auditory System Following Noise Overexposure: Contribution of TNF-α and IL-1β to the Pathogenesis of Hearing Loss.
The Role of Glia in the Peripheral and Central Auditory System Following Noise Overexposure: Contribution of TNF-α and IL-1β to the Pathogenesis of Hearing Loss.
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DOI：
10.3389/fnana.2017.00009
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发表时间：
2017
影响因子：
2.9
通讯作者：
Juiz JM
中科院分区：
文献类型：
--
作者：
Fuentes-Santamaría V;Alvarado JC;Melgar-Rojas P;Gabaldón-Ull MC;Miller JM;Juiz JM
重复的噪声暴露会诱导外周和中枢听觉系统的炎症和细胞适应，导致听力损失的病理生理学。在这项研究中，我们分析了噪声引起的炎症相关事件在耳蜗激活耳蜗核（CN），听觉通路的第一个中继站神经胶质介导的细胞反应的机制。在连续4天暴露于宽带噪声（0.5-32 kHz，118 dB SPL）4 h/d的大鼠中评估听觉功能、胶质激活、炎症介质的基因表达和蛋白质水平的改变以及胶质-神经元相互作用的超微结构变化，以诱导持久的听力损伤。暴露于噪声的大鼠产生了永久性的阈值偏移，这与毛细胞损失和反应性胶质细胞有关。噪声诱导的小胶质细胞激活在耳蜗中达到峰值1和10 D损伤后，其激活在CN更长的时间达到最大水平，在30 D后曝光。RT-PCR分析的炎症相关基因的表达在耳蜗表现出显着增加的mRNA表达水平的促炎和抗炎细胞因子，诱导型一氧化氮合酶，细胞间粘附分子和金属蛋白酶-1的组织抑制剂在1和10 D后曝光。在暴露于噪声的耳蜗中，白细胞介素-1 β（IL-1β）和肿瘤坏死因子α（TNF-α）在所有时间点均被反应性小胶质细胞、纤维细胞和神经元上调。然而，在CN中，神经元是这些细胞因子的唯一来源。这些观察结果表明，噪声暴露引起外周和中枢炎症反应，其中TNF-α和IL-1β参与调节噪声诱导的听力损失的发生和进展。
Repeated noise exposure induces inflammation and cellular adaptations in the peripheral and central auditory system resulting in pathophysiology of hearing loss. In this study, we analyzed the mechanisms by which noise-induced inflammatory-related events in the cochlea activate glial-mediated cellular responses in the cochlear nucleus (CN), the first relay station of the auditory pathway. The auditory function, glial activation, modifications in gene expression and protein levels of inflammatory mediators and ultrastructural changes in glial-neuronal interactions were assessed in rats exposed to broadband noise (0.5–32 kHz, 118 dB SPL) for 4 h/day during 4 consecutive days to induce long-lasting hearing damage. Noise-exposed rats developed a permanent threshold shift which was associated with hair cell loss and reactive glia. Noise-induced microglial activation peaked in the cochlea between 1 and 10D post-lesion; their activation in the CN was more prolonged reaching maximum levels at 30D post-exposure. RT-PCR analyses of inflammatory-related genes expression in the cochlea demonstrated significant increases in the mRNA expression levels of pro- and anti-inflammatory cytokines, inducible nitric oxide synthase, intercellular adhesion molecule and tissue inhibitor of metalloproteinase-1 at 1 and 10D post-exposure. In noise-exposed cochleae, interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) were upregulated by reactive microglia, fibrocytes, and neurons at all time points examined. In the CN, however, neurons were the sole source of these cytokines. These observations suggest that noise exposure causes peripheral and central inflammatory reactions in which TNF-α and IL-1β are implicated in regulating the initiation and progression of noise-induced hearing loss.