PROCESSES UNDERLYING DEAFNESS IN THE AUDITORY BRAINSTEM

听觉脑干中耳聋的潜在过程

• 批准号: 6312177
• 负责人: Avril Genene Holt
• 金额: $ 4.38万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6312177
• 关键词: auditory pathways; brain stem; deafness; gene expression; genetic mapping; immunocytochemistry; in situ hybridization; inferior colliculus; laboratory rat; microarray technology; neural information processing; neurotransmitters; postdoctoral investigator; somatostatin; western blottings

Deafness due to exposure to excess noise, ototoxic drugs, or as a natural consequence of aging, results in-malleable changes in the central auditory system. Studies of the IC and auditory cortex provide the most evidence for functional changes with deafness. However, there is also some evidence for deafness related changes in the superior olivary complex (SOC) including changes in neurotransmitter levels and binding. Preliminary data collected prior to this application, indicate significant changes in mRNA for GAD 65, 67 and the GABA alpha 1 receptor in the inferior colliculus (IC). These data are consistent with reports of age and noise related changes and reports of a role for GABA in functional changes. Interestingly, one of the greatest differences observed from preliminary data following deafening was in the neuropeptide somatostatin which has not been previously reported to play a role in deafness related plasticity. Therefore the goal of the proposed experiments is to identify and examine neurotransmission related genes within two regions of the central auditory system (IC, and SOC) before and after deafening with aminoglycosides. Deafness related changes in somatostatin production in the IC will be assessed with Western blots while in situ hybridization and immunocytochemisty will be used to determine regional and cell specificity. Using relatively new gene array technology, the final experiments will test the deafness related differential gene expression within the SOC and compare those changes with differential gene expression within the IC. Finally, by comparing gene expression at different time points following deafness the studies also will address the transience and permanence of the changes observed. Little is known regarding the effects of deafening on the adult central auditory system even with the widespread use of cochlear implants and other prosthetic devices. The proposed studies will lead to an understanding of how the central auditory system is modulated by deafness and will therefore aid in the development of prosthetic devices designed to facilitate the re-introduction of hearing in hearing impaired individuals.

由于暴露于噪音过多，耳毒性药物或衰老的自然结果，导致中央听觉系统上可差的变化。 IC和听觉皮层的研究为耳聋的功能变化提供了最大的证据。但是，还有一些证据表明，上橄榄络合物（SOC）的聋哑变化，包括神经递质水平和结合的变化。在此应用之前收集的初步数据表明，GAD 65、67的mRNA显着变化，而下丘（IC）中的GABA Alpha 1受体。这些数据与年龄和噪声相关的变化的报告以及GABA在功能变化中的作用的报告一致。有趣的是，震耳欲聋后的初步数据中观察到的最大差异之一是神经肽生长抑素，此前尚未据报道在与聋哑相关的可塑性中起作用。因此，拟议的实验的目的是在用氨基糖苷倾斜之前和之后识别和检查中央听觉系统（IC和SOC）的两个区域内的神经传递相关基因。将使用蛋白质印迹评估IC中生长抑制素的聋哑变化，而原位杂交和免疫细胞化学将用于确定区域和细胞特异性。使用相对较新的基因阵列技术，最终实验将测试SOC内的聋粒与差异基因表达，并将这些变化与IC内的差异基因表达进行比较。最后，通过在耳聋之后的不同时间点比较基因表达，研究还将解决观察到的变化的瞬态和永久性。即使广泛使用耳蜗植入物和其他假肢设备，聋人对成人中央听觉系统的影响知之甚少。拟议的研究将导致了解中央听觉系统如何通过耳聋调节，因此将有助于开发旨在促进听力重新引入听力障碍个人的假体设备。