Enhancement of olfactory neuron survival and targeting via odorant exposure

描述（申请人提供）：作为一名耳鼻喉科医生，我有丰富的嗅觉研究背景和嗅觉障碍临床评估经验，我有独特的机会将这两个学科结合起来寻找医学治疗方法。这项研究职业发展计划包括通过设计和实施拟议项目的五年指导培训。新技术、统计学、动物和人类研究伦理以及负责任的研究行为等课程将补充这一培训。塔夫茨大学医学院James Schwob博士的实验室将提供支持、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研究者，为患有嗅觉障碍的患者开发有效的治疗方法。

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.