PROPERTIES OF OLFACTORY RECEPTORS--NEURAL REGENERATION

每年有超过100万美国人遭受损害或伤害， 中枢神经系统（即，头部损伤、中风和脑肿瘤）。 在 此外，与衰老有关的疾病，如早老性痴呆， 老年痴呆症是一个严重的健康问题。 主要目标之一 神经科学的基础和临床研究的重点是寻找新的方法， 改善恢复和生活质量。 拟议的项目提供了一种手段，研究独特的过程， 神经发生和神经细胞替换发生在仓鼠 嗅觉系统 将使用两种程序来诱导 感觉神经元：神经横断和化学暴露。 后续 将使用定量方法研究神经发生和恢复， 确定替代神经元重建连接的能力 和中枢神经系统之间的联系并恢复其功能 后恢复 神经横断将在以下方面进行研究：1）解剖学研究， 确定替代神经元是否有能力恢复轴突 与嗅球中特定目标区域的连接，2） 电生理学研究，以确定重新连接的细胞的反应 （感受野和气味反应），和3）行为研究， 确定动物是否能感知并对感官刺激作出反应。 恢复 由于鼻腔暴露于环境因子（化学物质和 金属粉尘）也将在仓鼠中研究。 动物数据 实验将与人体解剖和外科病理学进行比较 研究发现，以调查细胞机制的基础鼻疾病。 一 发现仓鼠嗅觉系统的功能恢复 这表明，与目前的教条相反，神经元和 修复哺乳动物神经系统中受损的通路是可能的。 这项提议解决了关于神经元的潜力的重要问题。 中枢神经损伤的替代和功能修复 系统 嗅觉神经元的独特能力， 神经发生提供了研究这一过程的极好模型。 从拟议的实验结果可以提供一个显着的 神经再生领域的突破和发现可能有 直接临床应用。

Each year over one million Americans suffer from damage or injury to the central nervous system (i.e., head injury, stroke, and brain tumors). In addition, diseases related to aging such as presenile dementia and Alzheimer's Disease are a serious health problem. One of the major goals of basic and clinical research in the Neurosciences is to find new ways to improve recovery and quality of life. The proposed project provides a means of studying the unique process of neurogenesis and nerve cell replacement that takes place in the hamster olfactory system. Two procedures will be used to induce degeneration of sensory neurons: nerve transection and chemical exposure. Subsequent neurogenesis and recovery will be studied using quantitative methods to determine the capacity of replacement neurons to reestablish connections with the central nervous system and to restore function. Recovery after nerve transection will be investigated in: 1) Anatomical studies to determine if replacement neurons have the capacity to restore axon connections to specific target regions in the olfactory bulb, 2) Electrophysiological studies to determine the response of reconnected cells (receptive fields and odor response), and 3) Behavioral studies to determine if animals can detect and respond to sensory stimuli. Recovery from exposure of the nasal cavity to environmental agents (chemicals and metallic dusts) will also be investigated in the hamster. Data from animal experiments will be compared to human autopsy and surgical pathology findings to investigate cellular mechanisms underlying nasal disease. A finding that functional recovery occurs in the hamster olfactory system would suggest that, contrary to current dogma, replacement of neurons and repair of damaged pathways in the mammalian nervous system is possible. This proposal addresses important questions about the potential for neuron replacement and functional repair of damage within the central nervous system. The unique capacity of olfactory neurons for continued neurogenesis provides an excellent model in which to study this process. The results from the proposed experiments could provide a significant breakthrough for the field of neural regeneration and findings may have direct clinical application.