Enhancement of olfactory neuron survival and targeting via odorant exposure

通过气味暴露增强嗅觉神经元的存活和定位

• 批准号: 7079246
• 负责人: ERIC H HOLBROOK
• 金额: $ 18.92万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7079246
• 关键词: chemoreceptors; epithelium; human; innervation; neurons; olfactions; olfactory disorder; olfactory lobe; receptor

DESCRIPTION (provided by applicant): As an Otolaryngologist with a rich background in olfactory research and experience with the clinical assessment of olfactory disorders, I am positioned with the unique opportunity to combine these two disciplines in the search for medical therapies. This research career development plan consists of five years of mentored training through the design and implementation of the proposed project. Courses in new techniques, statistics, the ethics of animal and human studies, and the responsible conduct of research will supplement this training. The lab of Dr. James Schwob within Tufts University School of Medicine will provide the support, equipment, coursework, and overall educational environment to complete the research and training objectives of this proposal. My long-term career goal is to become an independent investigator within the area of olfaction at the Massachusetts Eye and Ear Infirmary in order to develop effective therapies for patients suffering from olfactory disorders. This research proposal will investigate the hypothesis that directed odorant exposure competitively enhances the survival and axonal targeting of receptor-specific olfactory neurons during recovery from lesion and that this effect occurs at the level of both the olfactory bulbs and olfactory epithelium. The hypothesis will be tested through three specific aims all utilizing the mouse model of recovery from methyl bromide exposure or olfactory nerve transection. Specific Aim 1 will look for the normalization in numbers of several different olfactory receptor subtypes within the epithelium after nares closure and will assess the effect of removing odor-induced activity on axon targeting. Specific Aim 2 will then show that selective repeated odorant exposure provides a competitive advantage in survival and axon targeting for the receptive olfactory neurons. Specific Aim 3 will then demonstrate that the enhanced survival observed in Specific Aim 2 can occur without the target organ and supports the role of CREB in this process. In summary, this proposal determines the effect of repeated odorant exposure on the recovery of the sense of smell after injury. It provides additional areas of research on the mechanisms of how the system attempts to heal itself, and most importantly, the information gained from this work is relevant for the development of therapies aimed at reversing sense of smell disorders in humans.

描述（由申请人提供）：作为一名具有丰富嗅觉研究背景和嗅觉障碍临床评估经验的耳鼻喉科医生，我有独特的机会将这两个学科联合收割机结合起来寻找医学疗法。该研究职业发展计划包括五年的指导培训，通过设计和实施拟议的项目。新技术，统计学，动物和人类研究的道德以及负责任的研究行为的课程将补充这种培训。塔夫茨大学医学院的James Schwob博士实验室将提供支持，设备，课程和整体教育环境，以完成本提案的研究和培训目标。我的长期职业目标是成为马萨诸塞州眼耳医院嗅觉领域的独立调查员，为嗅觉障碍患者开发有效的治疗方法。 这项研究计划将调查的假设，定向气味暴露竞争性增强的生存和轴突靶向的受体特异性嗅觉神经元在损伤恢复过程中，这种效果发生在嗅球和嗅上皮的水平。将通过三个具体目标对这一假设进行检验，所有目标均利用从甲基溴暴露或嗅觉神经切断中恢复的小鼠模型。具体目标1将寻找鼻孔闭合后上皮内几种不同嗅觉受体亚型数量的正常化，并将评估去除气味诱导的活性对轴突靶向的影响。具体目标2将表明，选择性重复气味暴露提供了一个竞争优势，在生存和轴突靶向的感受性嗅觉神经元。特异性目标3将证明特异性目标2中观察到的存活率提高可以在没有靶器官的情况下发生，并支持CREB在这一过程中的作用。 总之，该提案确定了重复接触气味剂对受伤后嗅觉恢复的影响。它提供了关于系统如何试图自我治愈的机制的额外研究领域，最重要的是，从这项工作中获得的信息与旨在逆转人类嗅觉障碍的疗法的开发有关。