REGENERATIVE PHENOMENA IN THE DEVELOPING ORGAN OF CORTI

柯蒂氏器官发育中的再生现象

基本信息

批准号：
6055808
负责人：
HANNA M SOBKOWICZ
金额：
$ 18.99万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-07-01 至 2002-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6055808
关键词：
developmental neurobiology disease /disorder model ear hair cell human tissue immunocytochemistry laboratory mouse model design /development nerve injury nervous system regeneration neural plasticity neuronal guidance newborn animals organ culture scanning electron microscopy sensorineural hearing loss

项目摘要

DESCRIPTION: The research concerns the morphological and biochemical events that lead o and accompany the regeneration/repair of the organ of Corti in cultures explanted from the neonatal mouse and injured by laser beam. Specifically, it is proposed to study: 1) Cellular interactions between injured hair cells and their supporting cells. Ultrastructural evidence indicate that supporting cells participate in hair cell survival and recovery. The study will attempt to elucidate if sprouting of supporting cells and wrapping on injured hair cells depends on a degree of hair cell damage (by varying intensity of laser beam) or the site of injury, targeted either at hair cell or selectivity at supporting cells; 2) Hair cell degeneration following laser ablation of their afferent neurons. Both hair cell death and damage have been observed upon the elimination of spiral neurons. The study aims to understand if these changes are caused by the process of laser irradiation that led tot he increase in voltage of membrane potential of the radial fibers or by the sudden denervation. The attenuation of the laser beam during the ablation and mechanical elimination of spiral neurons should help in distinguishing the factor that led to the secondary destruction of hair cells; 3) Selective destruction of hair cells by laser ablation of spiral neurons. The study raises provocative possibility of the trans-synaptic transfer of damage from the nerve cell to its target cell. By varying the site of ablated neurons we will try to induce the selective degeneration of inner versus outer hair cells; 4) Reinnervation of hair cells by collateral neuronal sprouting. It is expected that elimination of some spiral neurons will induce the collateral sprouting from the surviving ganglion cells. These experiments are designed to study the acquisition of new synaptic contacts; 5) Reformation of hair cell apical specializations after injury. The extent and constancy of hair cell repair will be examined: a) the regrowth of the stereociliary bundle will be studied by high resolution scanning electron microscope; b) the biochemical reconstruction of the hair cell cuticular plates will be examined by ultrastructural immunocytochemistry of the cytoskeletal proteins (in collaboration with N.B. Slepecky). A long-term goal of the project is to develop and in vitro model of defined reproducible injury to the hair cell in order to understand mechanism(s) and factors that lead to survival and recovery of the receptor cells. The significance of the research lies in bringing to light the plasticity of the mammalian hearing organs and identifying cellular processes that facilitate the preservation of its integrity.

描述：研究涉及形态和生化事件导致O并伴随Corti器官的再生/修复培养物从新生小鼠中散发出来，并由激光束受伤。具体而言，建议研究：1）受伤的毛细胞及其支撑细胞。超微结构证据表明支持细胞参与毛细胞的存活和恢复。该研究将尝试阐明是否发芽细胞和包裹受伤的毛细胞取决于一定程度的毛细胞损坏（通过激光束的强度不同）或受伤部位，针对性在毛细胞处或支持细胞时的选择性； 2）毛细单元激光消融其传入神经元后的变性。两头头发消除螺旋时已经观察到细胞死亡和损害神经元。该研究旨在了解这些变化是否是由激光照射的过程导致膜的电压增加径向纤维的潜力或突然的神经支配。这消融过程中激光束的衰减和机械消除螺旋神经元应有助于区分导致的因素毛细胞的次要破坏； 3）选择性破坏毛细胞通过激光消融螺旋神经元。这项研究提高了挑衅性从神经细胞到反式突触转移的可能性它的目标细胞。通过改变消融神经元的位置，我们将尝试诱导内毛和外毛细胞的选择性变性； 4）通过副神经元发芽来重新支配毛细胞。这是预计消除某些螺旋神经元将诱发抵押品从幸存的神经节细胞发芽。这些实验是设计的研究新的突触接触的获取； 5）头发改革受伤后的细胞顶特专业。头发的程度和恒定将检查细胞修复：a）立体捆绑包的再生将通过高分辨率扫描电子显微镜研究； b）毛细胞表皮板的生化重建将是通过细胞骨架蛋白的超微结构免疫细胞化学检查（与N.B. Slepecky合作）。该项目的长期目标是开发和体外定义模型为了了解机制和导致受体细胞存活和恢复的因素。这研究的意义在于揭示哺乳动物听力器官和识别促进的细胞过程维护其完整性。