PROPERTIES OF OLFACTORY RECEPTORS - NEURAL REGENERATION

嗅觉受体的特性 - 神经再生

• 批准号: 7091855
• 负责人: RICHARD M COSTANZO
• 金额: $ 22.35万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-12-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091855
• 关键词: aging; anosmia; behavior test; brain injury; chemoreceptors; genetically modified animals; laboratory mouse; nervous system regeneration; olfactions; olfactory lobe; olfactory nerve; synaptogenesis; synaptophysin

DESCRIPTION (provided by applicant): At present, little hope is offered to those with impaired olfactory function. The long-term objectives of this project are to investigate the mechanisms regulating neural regeneration and to develop strategies to enhance recovery and restore function following injury or disease. An established model of olfactory nerve injury will be used to investigate the role of MMPs following nerve injury and recovery processes during the regeneration and rewiring of olfactory axons in the olfactory bulb. Matrix metalloproteinases (MMPs) are regulators of the extracellular remodeling that occurs in reparative, homeostatic and metastatic processes. This study will determine if MMPs contribute to mechanisms that regulate the response to injury and regenerative and reparative processes in the olfactory system. Changes in MMP levels and their localization within the olfactory bulb will be measured at different time points from the onset of nerve injury, through degeneration, regeneration and recovery. It is hypothesized that MMP9 plays an important role during the early response to injury by regulating the amount of inflammation, gliosis, and scar formation and that MMP2 enhances recovery by facilitating the reinnervation and rewiring of axons in the olfactory bulb. MMP knockout mice will be used to determine if MMPs are required for normal recovery processes. Experiments represent a new direction and a novel approach that will begin to address the mechanisms of olfactory system regeneration and repair at the molecular level. The olfactory system may provide the key to understanding recovery processes in the central nervous system. Findings could lead to the development of new treatment strategies to help improve or restore olfactory function following injury or disease, and lay the groundwork for the future development of treatment strategies directed at modulating the activity of MMPs.

描述（由申请人提供）：目前，嗅觉功能受损的人几乎没有希望。该项目的长期目标是研究调节神经再生的机制，并制定策略，以促进损伤或疾病后的恢复和恢复功能。建立的嗅神经损伤模型将用于研究MMPs在嗅球中嗅轴突再生和重新布线过程中在神经损伤和恢复过程中的作用。基质金属蛋白酶（MMPs）是细胞外重塑的调节剂，发生在修复、稳态和转移过程中。这项研究将确定MMPs是否有助于调节嗅觉系统对损伤的反应以及再生和修复过程的机制。将在从神经损伤开始，通过变性、再生和恢复的不同时间点测量MMP水平的变化及其在嗅球内的定位。据推测，MMP 9通过调节炎症、神经胶质增生和瘢痕形成的量在对损伤的早期反应期间起重要作用，并且MMP 2通过促进嗅球中轴突的神经再支配和重新布线来增强恢复。MMP敲除小鼠将用于确定正常恢复过程是否需要MMP。实验代表了一个新的方向和一个新的方法，将开始解决嗅觉系统的再生和修复在分子水平上的机制。嗅觉系统可能是理解中枢神经系统恢复过程的关键。这些发现可能会导致新的治疗策略的开发，以帮助改善或恢复受伤或疾病后的嗅觉功能，并为未来开发针对调节MMPs活性的治疗策略奠定基础。