Investigation of a candidate chemotherapy-induced nausea sensory circuit

候选化疗引起的恶心感觉回路的研究

• 批准号: 8648406
• 负责人: Erika K. Williams
• 金额: $ 3.49万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648406
• 关键词: Adenovirus Vector; Adherence; Adverse effects; Afferent Neurons; Anatomy; Area; Basic Science; Behavior; Brain Stem; Calcium; Cells; Chemotherapy-Oncologic Procedure; Cisplatin; Coughing; Cues; Data; Detection; Development; Enteral; Enterochromaffin Cells; Esthesia; Feeding behaviors; Fiber; Food Poisoning; Foundations; Fright; Future; G-Protein-Coupled Receptors; Ganglia; Gastrointestinal tract structure; Gene Delivery; Generations; Genes; Genetic; Goals; Heart; Heart Rate; Image; Individual; Intestines; Investigation; Ligands; Liver; Lung; Malaise; Malignant Neoplasms; Maps; Mediating; Medical; Molecular; Morbidity - disease rate; Motion; Motor; Mus; Nausea; Neurons; Nucleus solitarius; Organism; Pancreas; Patients; Peripheral; Pharmaceutical Preparations; Physiological; Physiology; Population; Pregnancy; Prophylactic treatment; Quality of life; Reporter; Role; Sensory; Serotonin; Site; Stimulus; Stomach; Structure of area postrema; Symptoms; System; Testing; Therapeutic Intervention; Thymus Gland; Tissues; Toxin; Transgenic Mice; Upper digestive tract structure; Vagotomy; Vagus nerve structure; Vomiting; awake; blood pressure regulation; cancer therapy; chemotherapeutic agent; chemotherapy; clinically relevant; experience; gastrointestinal epithelium; in vivo; insight; mortality; nerve supply; neural circuit; prophylactic; public health relevance; receptor; recombinase; response; sensory system; serotonin receptor; tool; treatment planning; virus genetics

DESCRIPTION (provided by applicant): Chemotherapy-induced nausea negatively impacts quality of life, can alter adherence to chemotherapeutic treatment plans, and is repeatedly ranked as the greatest fear by patients beginning cancer treatment. The goal of this project is to better understand the sensory systems and molecular mechanisms involved in detection of stimuli leading to generation of nausea. We hope to define a molecularly unexplored sensory circuit and its role in modulating organism behavior and physiology. The most efficacious anti-nausea medication class target serotonin receptors preferentially expressed in the sensory component of the vagus nerve. However, the anatomical distribution of innervation by these fibers remains unknown, as does the effect of manipulating this circuitry on behavior. I will use genetic tools including mouse transgenic lines and adenoviral vector gene delivery to specifically map the anatomy and functionally manipulate candidate nausea circuits. Examination of this system will open basic research into a poorly characterized and clinically relevant sensory system, and also provide potential alternative targets for therapeutic intervention of high relevance to many patients.

描述（由申请人提供）：化疗引起的恶心会对生活质量产生负面影响，可能会改变对化疗治疗计划的依从性，并且多次被列为开始癌症治疗的患者最担心的事情。该项目的目标是更好地了解导致恶心产生的刺激检测所涉及的感觉系统和分子机制。我们希望定义一个分子上未经探索的感觉回路及其在调节有机体行为和生理学中的作用。最有效的抗恶心药物类别针对优先在迷走神经的感觉成分中表达的血清素受体。然而，这些纤维的神经支配的解剖学分布仍然未知，操纵该电路对行为的影响也是未知的。我将使用包括小鼠转基因系和腺病毒载体基因传递在内的遗传工具来专门绘制解剖图并在功能上操纵候选恶心回路。对该系统的检查将开启对特征较差且临床相关的感觉系统的基础研究，并且还为与许多患者高度相关的治疗干预提供潜在的替代目标。