CELLULAR PROCESSES OF CENTRAL AUDITORY NEURONAL DEATH

中枢听觉神经元死亡的细胞过程

• 批准号: 6476073
• 负责人: DIANNE none DURHAM
• 金额: $ 26.45万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6476073
• 关键词: Aves; adenosinetriphosphatase; afferent nerve; age difference; auditory nuclei; auditory pathways; bioenergetics; cell death; cell proliferation; cellular pathology; central nervous system; chick embryo; cochlea; denervation; ear hair cell; enzyme activity; gentamicins; histochemistry /cytochemistry; mitochondria; neural information processing; neurons; noise; oxidative phosphorylation; stainings; tissue /cell culture

DESCRIPTION: (Adapted from the Investigator's Abstract) Damage to the inner ear can occur from a variety of causes, including diseases, noise and ototoxic drugs. Prolonged damage to the cochlea can have lasting and often detrimental effects on auditory neurons in the CNS because these neurons rely on continuous afferent input for normal function. Interactions between the periphery; and the CNS have been studied extensively in the avian auditory system. Auditory neurons in the cochlear nucleus (n. magnocellularis, NM) receive their only excitatory input from the cochlea via the eighth nerve. Destruction of the cochlea in hatchling chickens sets in motion a series of rapid metabolic changes in postsynaptic NM neurons, including upregulation of oxidative function. Within several days, 30% of NM neurons will die and the remainder show long-lasting decreases in metabolic activity. When the cochlea is damaged in an adult chicken, the extent of the response in NM varies with the breed of animal. In mammals damage to the cochlea is permanent. However, birds have the remarkable capacity to replace damaged cochlear hair cells. Repair begins within several days of damage, and anatomical recovery s followed by the return of substantial auditory function. Although the mechanisms of cochlear recovery have been examined extensively, much less is known about how the CNS responds to hair cells loss and regeneration. In hatchling birds we will examine how NM neurons respond to reversible loss of cochlear function caused by gentamicin. We will evaluate how the number of NM neurons changes following gentamicin damage to the cochlea, and determine whether a reversible oxidative upregulation occurs. We will determine whether new neurons are generated in NM similar to the replacement of cochlear hair cells. In adult birds we will test the hypothesis that differences in cochlear function underlie the different CNS responses to cochlear ablation in birds of different breeds. We will evaluate whether adult birds differ in their response to environmental noise, and whether CNS responses can be predicted by cochlear integrity. Finally, we will evaluate the capacity for hair cell regeneration in adult birds. Our ability to repair damage to the cochlea is continuously improving, with advances in cochlear implant technology and the possibility for regeneration of mammalian cochlear hair cells. These advances in peripheral repair make it all the more crucial to assess the functional capacity of the auditory CNS.

描述：（改编自研究者摘要）内耳损伤 可由多种原因引起，包括疾病、噪音和耳毒性 毒品对耳蜗的长期损害可能会造成持久的， 对中枢神经系统中的听觉神经元的影响，因为这些神经元依赖于连续的 正常功能的传入输入。外围国家与 CNS在鸟类听觉系统中已被广泛研究。听觉 耳蜗核中的神经元（n. magnocellularis，NM）只接受他们的 来自耳蜗的兴奋性输入通过第八神经。破坏 小鸡的耳蜗启动了一系列快速的代谢过程 突触后NM神经元的变化，包括氧化 功能在几天内，30%的NM神经元将死亡，其余的神经元将死亡。 表现出代谢活性的长期下降。当耳蜗受损时 在成年鸡中，NM的反应程度随品种而变化， 动物 哺乳动物耳蜗的损伤是永久性的。然而，鸟类有 它具有替代受损耳蜗毛细胞的非凡能力。修复开始 在损伤后的几天内，解剖恢复，然后返回 具有实质性的听觉功能。虽然耳蜗恢复的机制 虽然已经进行了广泛的研究，但对中枢神经系统的反应知之甚少。 毛细胞的损失和再生。在幼鸟，我们将研究如何NM 神经元对由庆大霉素引起的耳蜗功能的可逆性丧失作出反应。 我们将评估庆大霉素后NM神经元数量的变化 损伤的耳蜗，并确定是否可逆的氧化 发生上调。我们将确定新的神经元是否产生在NM 类似于耳蜗毛细胞的替换。在成年鸟类中，我们将测试 耳蜗功能差异是中枢神经系统不同的基础这一假说 不同品种鸟类耳蜗消融的反应。我们将评估 成年鸟类对环境噪音的反应是否不同， 是否可以通过耳蜗完整性预测CNS反应。最后我们将 评估成年鸟类毛细胞再生的能力。 我们修复耳蜗损伤的能力正在不断提高， 人工耳蜗技术的进步和再生的可能性 哺乳动物耳蜗毛细胞。外周修复的这些进展 对评估听觉中枢神经系统的功能能力更为重要。