Physiological Studies of Age-Related Hearing Loss

年龄相关性听力损失的生理学研究

• 批准号: 7030960
• 负责人: RICHARD A SCHMIEDT
• 金额: $ 24.95万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7030960
• 关键词: acoustic nerve; action potentials; aging; cell proliferation; cochlear microphonic potentials; ear hair cell; electrophysiology; electrostimulus; fiber cell; furosemide; gap junctions; gerbil /jird; hearing disorders; homeostasis; inhibitor /antagonist; injection /infusion; microelectrodes; neuropharmacology; otoacoustic emission; presbycusis; sound; stressor

DESCRIPTION (provided by applicant): A major factor in human and animal presbyacusis is the degeneration of the cochlear lateral wall tissues and stria vascularis. These tissues supply energy to the organ of Corti in the form of the endocochlear potential (EP). In young animals, this 90 mV potential has been shown to be of fundamental importance in the operation of the cochlear amplifier and subsequent determination of auditory thresholds. Gerbils aged in quiet show an age-related decline of EP, the basis of metabolic presbyacusis. Over the last grant cycle we have developed a model of the aged ear in young gerbils using the chronic application of furosemide to the cochlea to block the generation of the EP. Here we further explore the effects of acute and chronic EP manipulation on cochlear transduction and the encoding of sound in auditory-nerve fibers. Moreover, we explore cell replication as a possible mechanism fundamental to the EP decline with age. There are three specific aims. Specific Aim 1 examines the effects of EP modulation by direct current injection into the scala media of normal, EP-impaired, and aged cochleas. This aim will test the hypothesis that EP is the primary factor controlling neural thresholds and otoacoustic emissions. Moreover, it tests whether direct current injection can serve to ameliorate metabolic presbyacusis. Specific Aim 2 focuses on how populations of auditory-nerve fibers respond to EP decline, with specific regard to the thresholds of low- and high-spontaneous rate (SR) fibers. This aim tests the hypothesis that the thresholds of low-SR fibers located in the cochlear base are more sensitive to EP decline than corresponding high-SR fibers. It will also examine the characteristics of these fibers with acoustic stimuli in EP-impaired cochleas. Specific Aim 3 investigates the role of lateral wall fibrocytes in the production and maintenance of the EP. The hypothesis is that fibrocyte proliferation is essential for EP homeostasis, and a reduced rate of replication is the basis for the decline in EP observed in aged animals. These experiments will involve the infusion of mitotic inhibitors and gap junction uncouplers into the cochlea. Taken together, the three aims explore the major causes and effects of metabolic presbyacusis and have direct application to future interventions to help restore age-related hearing loss.

描述（由申请人提供）：人类和动物长老会的主要因素是人工耳蜗侧壁组织和血管血管的变性。这些组织以内核势（EP）的形式向Corti的器官提供能量。在年轻动物中，这种90 mV的电位已被证明在人工耳蜗放大器的运行中至关重要，随后确定听觉阈值。在安静中衰老的沙尔比尔斯（Gerbils）表明，EP的年龄相关，这是代谢长老会的基础。在上一个赠款周期中，我们使用速尿中的长期应用在耳蜗中开发了年轻的幼鼠的老年耳朵模型，以阻止EP的产生。在这里，我们进一步探讨了急性和慢性EP操纵对耳蜗转导的影响以及在听觉神经纤维中声音的编码。此外，我们探索细胞复制是随着年龄的增长而基础下降的可能机制。有三个特定的目标。具体目标1通过直接电流注入正常，EP损伤和老化的耳蜗的晶格来检查EP调制的影响。该目标将检验以下假设：EP是控制神经阈值和耳声排放的主要因素。此外，它测试了直流注射是否可以改善代谢长老会。具体目标2的重点是听觉神经纤维的种群如何应对EP下降，具体考虑了低自发率（SR）纤维的阈值。该目标检验了以下假设：与相应的高SR纤维相比，位于人工耳蜗的低SR纤维的阈值对EP下降更敏感。它还将检查这些纤维在EP受损的耳蜗中具有声刺激的特征。具体目标3研究了侧壁纤维细胞在EP的生产和维持中的作用。假设是纤维细胞增殖对于EP稳态至关重要，而复制率降低是老年动物观察到的EP下降的基础。这些实验将涉及将有丝分裂抑制剂和间隙连接器输注到耳蜗中。综上所述，这三个目标探讨了代谢长老会的主要原因和影响，并直接适用于将来的干预措施，以帮助恢复与年龄相关的听力损失。