REGENERATIVE PHENOMENA IN THE DEVELOPING ORGAN OF CORTI

柯蒂氏器官发育中的再生现象

• 批准号: 2014422
• 负责人: HANNA M SOBKOWICZ
• 金额: $ 21.06万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2014422
• 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

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：研究涉及形态学和生化事件 导致并伴随Corti器官的再生/修复， 从新生小鼠中分离培养并经激光束损伤。 具体而言，建议研究：1）细胞之间的相互作用 受损的毛细胞及其支持细胞。 超微结构证据 表明支持细胞参与毛细胞存活， 复苏 这项研究将试图阐明， 毛细胞和受伤的毛细胞的包裹取决于毛细胞的程度 损伤（通过改变激光束的强度）或损伤部位，目标 毛细胞或支持细胞的选择性; 2）毛细胞 在激光消融其传入神经元后的变性。 都是头发 已经观察到细胞死亡和损伤在消除螺旋后 神经元 这项研究旨在了解这些变化是否是由 激光辐照导致膜电压升高的过程 放射状纤维的电位或突然去神经支配。 的 在烧蚀和机械消除期间激光束的衰减 螺旋神经元的数量应该有助于区分导致 毛细胞的继发性破坏; 3）毛细胞的选择性破坏 通过激光切除螺旋神经元 这项研究引发了争议 损伤从神经细胞跨突触转移到 它的靶细胞。 通过改变消融神经元的位置，我们将尝试 诱导内毛细胞相对于外毛细胞的选择性变性; 4） 侧支神经元发芽对毛细胞的神经再支配。 是 预计消除一些螺旋神经元将诱导侧支循环， 从存活的神经节细胞中长出 这些实验是为了 研究新的突触接触的获得; 5）毛发的重建 损伤后的细胞顶端特化。 毛发的范围和恒定性 将检查细胞修复：a）静纤毛束的再生长 将通过高分辨率扫描电子显微镜进行研究; 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 (in与NB合作Slepecky）。 该项目的一个长期目标是开发和定义体外模型 对毛细胞的可再现损伤，以了解机制， 导致受体细胞存活和恢复的因素。 的 研究的意义在于揭示了 哺乳动物的听觉器官和识别细胞过程， 保持其完整性。