NEUROBIOLOGY OF VERTEBRATE OLFACTORY MUCOSA

计划项目的这一部分由两个部分组成： 临床研究和基础科学研究。该计划的具体目标是 临床研究是为了确定吸入可卡因对 含有化学感受器的人鼻粘膜 嗅觉系统的一部分。基础科学的具体目的 研究是为了检验微绒毛细胞或 遍及人类呼吸道的“刷状细胞” 有些哺乳动物是化学感受器。滥用可卡因是一种 迅速增长的流行比例的主要健康问题。 尽管收集了大量关于可卡因滥用的数据，但 我们的知识存在着显著的差距：什么是 可卡因滥用对人鼻部组织病理学的影响 粘膜及其独特的嗅觉感受器神经元群？ 嗅觉粘膜含有几百万个嗅觉感受器 神经元，每个神经元都是一个初级感觉细胞--一个双极神经元， 其细胞体位于嗅觉上皮中，这就发出了一个 树突进入鼻腔和至嗅球的轴突 大脑。这些“裸露的神经元”恰好位于 中枢神经系统，是人体内唯一的神经细胞 与环境直接接触的物质。因此， 他们与吸入的可卡因直接接触。嗅觉 与其他神经组织不同，粘膜可以安全地在 局部麻醉和电子显微镜检查，并将 拆卸后重新生成。因此，这个项目将调查 可卡因滥用对人类嗅觉影响的组织病理学研究 受体，这将成为一个主要的模型系统 可卡因及其混伪品对细胞超微结构的影响 人类中枢神经系统的组成部分。嗅觉 人类和许多哺乳动物的上皮含有纤毛双极 嗅觉神经元和微绒毛细胞。最近的证据 说明微绒毛细胞是感觉神经元。因此， 人类的嗅觉粘膜似乎包含两个 在形态上不同类别的嗅觉感受器细胞。什么时候 在电子显微镜下观察，微绒毛细胞 嗅黏膜显示一种惊人的超微结构 与气管中发现的“刷状细胞”相似， 细支气管，甚至人类、大鼠肺深处的肺泡， 和其他哺乳动物物种。使用示踪剂技术 研究，计算机生成的三维重建通过 高压电子显微镜和免疫细胞化学，这是 项目将测试刷状细胞发现的假设 整个呼吸系统本质上都是化学感受性的。

This portion of the Program Project consists of two components: clinical studies and basic science studies. The specific aim of the clinical studies is to determine the effects of inhaled cocaine on the human nasal mucosa that contains the chemosensory receptors of the olfactory system. The specific aim of the basic science studies is to test the hypothesis that the microvillar cells, or "brush cells", found throughout the respiratory tract of humans and some mammals are chemoreceptors. Cocaine abuse is a rapidly-growing major health problem of epidemic proportions. Despite the wealth of data gathered on cocaine abuse, a significant gap in our knowledge exists: what are the histopathological effects of cocaine abuse on the human nasal mucosa and its unique population of olfactory receptor neurons? The olfactory mucosa contains several million olfactory receptor neurons, each of which is a primary sense cell--a bipolar neuron, whose cell body sits in the olfactory epithelium, that sends a dendrite into the nasal cavity and an axon to the olfactory bulb of the brain. These "naked neurons" sit right at the frontier of the central nervous system, and are the only nerve cells in the body that make direct contact with the environment. Consequently, they make direct contact with inhaled cocaine. The olfactory mucosa, unlike other nervous tissue, can be safely biopsied under local anesthesia and examined by electron microscopy, and will regenerate after removal. Therefore, this project will investigate the histopathology of cocaine abuse upon human olfactory receptors, which will serve as a major model system for the effects of cocaine and its adulterants upon the ultrastructure of components of the human central nervous system. The olfactory epithelium of humans and many mammals contains ciliated bipolar olfactory neurons and microvillar cells. Recent evidence indicates the microvillar cells are sensory neurons. Consequently, it seems that the human olfactory mucosa contains two morphologically distinct classes of olfactory receptor cell. When viewed by electron microscopy, the microvillar cells in the olfactory mucosa demonstrate a striking ultrastructural resemblance to the "brush cells" that are found in the trachea, bronchioles, and even alveoli deep in the lungs of humans, rats, and other mammalian species. Using the techniques of tracer studies, computer-generated three-dimensional reconstruction by high voltage electron microscopy, and immunocytochemistry, this project will test the hypothesis that the brush cells found throughout the respiratory system are chemoreceptive in nature.