Olfactory neurons from bipolar patients

描述：（由申请人提供）该提案寻求一个结构化的研究培训计划，这将使 Chang-Gyu Hahn 能够成为可能。医学博士 博士成为一名独立研究者，因为他展示了嗅觉受体神经元 (ORN) 在检查双相情感障碍的神经生物学方面的实用性。 职业目标和目标：职业目标是能够通过以下方式将最先进的分子技术应用于临床相关的研究范式 在ORN系统中，他提出了一个重点关注以下领域的职业发展计划。 1) 人类 ORN 系统的离子成像和神经生物学；2) 单细胞反义 RNA 扩增技术。 职业发展活动：候选人将接受人类嗅觉神经元离子成像（由共同导师 Nancy Rawson，PILD 指导）和单细胞分子技术（由共同导师 James Eberwine 博士指导）方面的专门培训。博士。 Karl Rickels 将为具体目标 2 的治疗结果研究部分提供个人监督。Robert H. Lenox 博士将通过整合正式课程、实验室会议和监督来监督职业发展计划。 背景：ORN 是唯一可通过嗅上皮活检获得的中枢神经系统神经元，为研究活体神经元中的分子事件提供了独特的机会。通过在疾病的特定阶段获取 ORN，结合对患者的纵向随访，神经元中分子事件的病理生理学意义可以与双相情感障碍联系起来。 假设：我们的初步数据表明，双相情感障碍中细胞内钙对odbrants的反应发生了改变。 I) ORN 对气味剂的细胞内钙反应主要降低，这是双相情感障碍的一个特征。 2) 双相情感障碍患者 ORN 中 ICa 反应降低是由于参与钙流动的基因表达改变所致。 3）锂处理后，对气味刺激有反应的 ORN 的百分比总体下降。 4) 来自双相情感障碍患者的外植体培养物中的 ORN 将显示与患者体内 ORN 相似的 ICa 反应。 具体目标： 1) 表征双相情感障碍患者 ORN 中 ICa 稳态和基因调控的特征和情绪状态依赖性改变。 2) 确定锂治疗后 ICa 稳态的治疗相关变化。 3) 使用气味诱导的 ICa 反应来表征双相情感障碍患者的 ORN 培养物。

DESCRIPTION: (provided by applicant) This proposal seeks a structured research training program, which will enable Chang-Gyu Hahn. M.D. Ph.D. to become an independent investigator as he demonstrates the utility of olfactory receptor neurons (ORNs) to examine the neurobiology underlying bipolar disorder. Career Goals and Objectives: With the career goat of being able to apply the most advanced molecular techniques to clinically relevant research paradigms through the ORN system, he proposes a career development plan focusing on following areas. 1) ionic imaging and the neurobiology of the human ORN system and 2) Single cell antisense RNA amplification technique. Career Development Activities: The candidate will receive specialized training in ionic imaging in human olfactory neurons (guided by Nancy Rawson, PILD, co-mentor) and in single cell molecular technique (supervised by James Eberwine, Ph.D., co-mentor). Dr. Karl Rickels will provide individual supervision for the treatment outcome study component of the specific aim 2. Dr. Robert H. Lenox will oversee the career development program through integrating formal courses, lab meetings and supervisions. Background: ORNs, the only CNS neurons that are obtainable through olfactory epithelial biopsy, provide a unique opportunity to investigate molecular events in neurons from living subjects. By obtaining ORNs during specific stages of the illness, in conjunction with a longitudinal follow-up of patients, pathophysiologic significance of molecular events in neurons can be linked to bipolar disorder. Hypothesis: Our preliminary data suggest that intracellular calcium responses to odbrants are altered in bipolar disorder. I) Intracellular calcium responses of ORNs to odorants are predominantly a decrease as a trait of bipolar disorder. 2) The decreased ICa responses in ORNs from bipolar patients are due to altered expression of the genes that are involved in calcium flux. 3) The percentage of ORNs that respond to odorant stimulation is overall decreased following lithium treatment. 4) ORNs in explant cultures from bipolar patients will show similar ICa responses as in vivo ORNs of patients. Specific Aims: 1) To characterize trait- and mood state- dependent alterations in ICa homeostasis and gene regulation in ORNs from bipolar patients. 2) To identify therapeutically relevant changes in ICa homeostasis following lithium treatment. 3) To characterize ORN cultures from bipolar patients using odorant induced ICa responses.