Data_Sheet_1_Resveratrol prevents hearing loss and a subregion specific- reduction of serotonin reuptake transporter induced by noise exposure in the central auditory system.PDF

Prolonged or excessive exposure to noise can lead to hearing loss, tinnitus and hypersensitivity to sound. The effects of noise exposure on main excitatory and inhibitory neurotransmitter systems in auditory pathway have been extensively investigated. However, little is known about aberrant changes in neuromodulator systems caused by noise exposure. In the current study, we exposed 2-month-old mice to a narrow band noise at 116 dB SPL for 6 h or sham exposure, assessed auditory brainstem responses as well as examined the expression of serotonin reuptake transporter (SERT) in the cochlear nucleus (CN), inferior colliculus (IC), and primary auditory cortex (Au1) using immunohistochemistry. We found that noise exposure resulted in a significant increase in hearing thresholds at 4, 8, 16, 24, and 32 kHz, as well as led to a significant reduction of SERT in dorsal cochlear nucleus (DCN), dorsal IC (ICd), external IC (ICe), and Au1 layers I-IV. This reduction of SERT in these subregions of central auditory system was partially recovered 15 or 30 days after noise exposure. Furthermore, we examined efficacy of resveratrol (RSV) on hearing loss and loss of SERT induced by noise exposure. The results demonstrated that RSV treatment significantly attenuated threshold shifts of auditory brainstem responses and loss of SERT in DCN, ICd, ICe, and Au1 layers I-IV. These findings show that noise exposure can cause hearing loss and subregion-specific loss of SERT in the central auditory system, and RSV treatment could attenuate noise exposure-induced hearing loss and loss of SERT in central auditory system.

长期或过度暴露于噪声环境，可引发听力损失、耳鸣及听觉超敏反应。目前学界已针对噪声暴露对听觉通路内主要兴奋性与抑制性神经递质系统的影响开展了大量研究。然而，针对噪声暴露所引发的神经调质系统异常变化，目前仍知之甚少。本研究中，我们将2月龄小鼠暴露于116 dB声压级（SPL）的窄带噪声中6小时，同时设置假暴露对照组；采用免疫组织化学法，检测听觉脑干反应（auditory brainstem responses），并分析耳蜗核（cochlear nucleus, CN）、下丘（inferior colliculus, IC）以及初级听觉皮层（primary auditory cortex, Au1）内5-羟色胺再摄取转运体（serotonin reuptake transporter, SERT）的表达情况。研究结果显示，噪声暴露可使小鼠在4、8、16、24及32 kHz频率下的听阈显著升高，同时导致背侧耳蜗核（dorsal cochlear nucleus, DCN）、背侧下丘（dorsal IC, ICd）、外侧下丘（external IC, ICe）以及Au1第I-IV层内的SERT表达量显著降低。在噪声暴露后15天或30天，中枢听觉系统上述亚区的SERT表达降低现象可得到部分恢复。此外，我们探究了白藜芦醇（resveratrol, RSV）对噪声暴露诱导的听力损失及SERT表达降低的干预效果。结果表明，白藜芦醇干预可显著减轻听觉脑干反应的听阈偏移，并缓解DCN、ICd、ICe及Au1第I-IV层内的SERT表达降低情况。本研究结果证实，噪声暴露可引发听力损失及中枢听觉系统亚区特异性的SERT表达降低，而白藜芦醇干预能够有效减轻噪声暴露诱导的听力损失与中枢听觉系统内的SERT表达降低现象。