低强度噪声对发育早期耳蜗传入神经支配的损伤及长期后果

Noise exposure is one of the most common causes of sensorineural hearing loss. It has been identified that noise exposure at low levels that do not cause permanent threshold shift can damage the afferent innervations to the cochlea in adult animals and deteriorate temporal processing ability of the cochlea, suggesting that the safety of noise exposure cannot be simply defined by the permanent threshold shift. On the other hand, it is also clear now that hearing loss can speed up the development of dementia, indicating the effect of hearing loss outside auditory system. Since individuals are generally more vulnerable to lesion factors, this project is designed to verify if the low-level noise exposure during early development will exert severer impairment to the afferent innervation of the cochlea that can extend to the adulthood, to analyze the molecular mechanisms of such impairment and the impact on cochlear signal processing. Without hearing threshold change, the damage to the cochlear afferent innvervation will significantly reduce the cochlear output to the brain. Therefore, we will further investigate if such reduction of cochlear output that starts in early development will impair the development of auditory brain as well as the brain region that is important for learning and memory. This project will reveal the impact of low-level noise from both the damaging mechanisms to peripheral auditory organ as well as the central consequences, especially when the exposure occurs during early development. The outcome of this project will help to provide scientific data for noise safety standard for perinatal and postnatal subjects.

噪声暴露是获得性感音神经性聋的主要原因之一。研究发现，不引起永久性听觉阈值改变的低强度噪声暴露在成年动物可破坏耳蜗传入神经支配并导致耳蜗时间编码能力减退；提示噪声安全性不能单纯根据是否有阈值升高来界定。另外,已确定听力损失可加速智障的发展；提示听力损失的有害性不局限于听觉系统内部。由于发育早期机体一般对伤害性因素更为敏感，本研究将确定在听觉发育早期的低强度噪声暴露是否对耳蜗传入神经支配产生更为严重的、延续到成年的损伤效应，并分析这种损伤的分子机制和对成年后耳蜗信号处理能力的影响。在听觉阈值不变的条件下，耳蜗传入神经支配的损伤将减弱耳蜗对中枢的信号输入。进一步我们将研究听觉发育早期此种外周输入的减弱是否对学习认知能力的发育产生长期影响。本项目将从外周损伤机制和中枢长期效应两个方面扩展对低强度噪声损伤，特别是发育早期损伤危害性的认识，为制定围产期和新生儿噪声安全标准提供科学依据。

噪声暴露是获得性感音神经性聋（sensorineural hearing loss，SNHL）的主要原因之一。根据传统观念，听觉阈值的改变（阈移）是临床上判断噪声性听觉损伤的主要根据；是否导致听觉阈值升高也是噪声安全标准的主要制定依据。研究发现，不引起永久性听觉阈值(permanent threshold shift, PST)改变的低强度噪声暴露在成年动物可破坏耳蜗传入神经支配并导致耳蜗时间编码能力减退；提示噪声安全性不能单纯根据是否有阈值升高来界定。另外,已确定听力损失可加速智力障碍的发展；提示听力损失的有害性不局限于听觉系统内部。由于发育早期机体对伤害性因素更为敏感，本项目全面研究了持续低强度噪声对耳蜗发育期小鼠听觉功能和学习记忆能力的损伤以及对这些损伤的潜在机制的分析,并在以下几个方面取得了重要进展：（1）确立了低强度噪声连续多次暴露在耳蜗发育期小鼠可以产生“隐性”听力损伤； （2）证实IHC-SGN突触在噪声损伤后有一定程度的修复，提示发育期突触具有可塑性改变的潜在能力；（3）伴随突触形态修复，听觉功能出现多项不利改变，提示修复的突触在功能上的不完全修复；（4）噪声组动物在学习和记忆能力上表现出功能减退的现象与耳蜗功能的改变具有相关性。上述成果明确了耳蜗功能发育期给予低强度噪声持续暴露可导致隐性听力损伤的可能性，以及这种听觉功能损伤与学习记忆能力下降之间关系。由于低强度噪声见于日常生活，对个体的影响不仅体现在听觉功能的改变，而且对个体的学习记忆能力存在潜在的影响。本研究的结果第一次分析了耳蜗发功能育期的低强度噪声导致学习记忆能力的损伤与听觉功能之间的之间关系，本研究的成果为今后的深入研究奠定了坚实的基础。