PROPERTIES OF OLFACTORY RECEPTORS - NEURAL REGENERATION

嗅觉受体的特性 - 神经再生

• 批准号: 7853393
• 负责人: RICHARD M COSTANZO
• 金额: $ 10.98万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7853393
• 关键词: Address; Affect; Attenuated; Axon; Brain; Cells; Cicatrix; Development; Disease; Extracellular Matrix; Future; Gelatin Zymography; Gelatinase B; Glial Fibrillary Acidic Protein; Gliosis; Growth Associated Protein 43; Immunohistochemistry; Inflammation; Injury; Knock-out; Knockout Mice; Lead; MMP2 gene; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Measures; Methods; Modeling; Molecular; Mus; Natural regeneration; Nerve; Nerve Regeneration; Neuraxis; Neuroglia; Olfactory Nerve; Pathway interactions; Play; Process; Property; Proteins; Recovery; Research; Research Personnel; Role; Severities; Spinal Cord; Stromelysin 1; Structure; System; Testing; Time; Tissues; Western Blotting; extracellular; functional restoration; improved; improved functioning; insight; metastatic process; nerve injury; nervous system disorder; novel strategies; olfactory bulb; olfactory receptor; programs; regenerative; reinnervation; repaired; research study; response to injury; restoration; treatment strategy

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.

目前，嗅觉功能受损的人几乎没有希望。这个项目的长期目标是 该项目的目的是研究神经再生的调节机制，并制定策略 促进受伤或疾病后的恢复和功能恢复。一种已建立的嗅神经模型 损伤将被用来研究MMPs在神经损伤和恢复过程中的作用 嗅球内嗅觉轴突的再生和重新连接。基质金属蛋白酶(MMPs)是 修复、内稳态和转移过程中发生的细胞外重构的调节者。 这项研究将确定MMPs是否有助于调节对伤害的反应和 嗅觉系统中的再生和修复过程。基质金属蛋白酶水平的变化及其定位 在嗅球内将测量从神经损伤开始的不同时间点，通过 退化、再生和恢复。据推测，MMP9在体内发挥着重要作用。 通过调节炎症、胶质增生和瘢痕形成的数量以及MMP2对损伤的早期反应 通过促进嗅球内轴突的再神经支配和重新布线来促进康复。明尼苏达 基因敲除小鼠将被用来确定正常恢复过程是否需要MMPs。实验 代表了一个新的方向和新的方法，将开始解决嗅觉的机制 在分子水平上的系统再生和修复。嗅觉系统可以提供 了解中枢神经系统的恢复过程。这些发现可能会导致 新的治疗策略，帮助改善或恢复受伤或疾病后的嗅觉功能，并奠定 为今后制定旨在调节MMPs活性的治疗策略奠定基础。

项目成果

Continual neurogenesis of vomeronasal neurons in vitro.

体外犁鼻神经元的持续神经发生。

• 发表时间: 1999
• 期刊: Journal of neurobiology
• 作者: Osada,T;Ikai,A;Costanzo,RM;Matsuoka,M;Ichikawa,M
• 通讯作者: Ichikawa,M

A new surgical approach to the study of vomeronasal system regeneration.

研究犁鼻系统再生的新手术方法。

• DOI: 10.1093/chemse/bjh148
• 发表时间: 2005
• 期刊: Chemical senses
• 影响因子: 3.5
• 作者: Matsuoka,Masato;Norita,Masao;Costanzo,RichardM
• 通讯作者: Costanzo,RichardM

Grafting the olfactory epithelium to the olfactory bulb.

将嗅上皮移植到嗅球上。

• DOI: 10.2500/ajra.2009.23.3307
• 发表时间: 2009
• 期刊: American journal of rhinology & allergy
• 影响因子: 2.6
• 作者: Yagi,Sayaka;Costanzo,RichardM
• 通讯作者: Costanzo,RichardM

Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy.

轴索切除术后嗅上皮变性和再生的扫描电子显微镜研究。

• DOI: 10.1007/bf01190842
• 发表时间: 1989
• 期刊: Journal of neurocytology
• 作者: Morrison,EE;Costanzo,RM
• 通讯作者: Costanzo,RM

A comparative immunocytochemical study of development and regeneration of chemosensory neurons in the rat vomeronasal system.

大鼠犁鼻系统化学感应神经元发育和再生的比较免疫细胞化学研究。

• DOI: 10.1016/s0006-8993(02)02823-8
• 发表时间: 2002
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Matsuoka,Masato;Osada,Toshiya;Yoshida-Matsuoka,Junko;Ikai,Atsushi;Ichikawa,Masumi;Norita,Masao;Costanzo,RichardM
• 通讯作者: Costanzo,RichardM