Investigating the Critical Role of Glia In Peripheral Organ Development and Physiology

研究神经胶质细胞在周围器官发育和生理学中的关键作用

• 批准号: 10676501
• 负责人: Sarah Elisabeth Williams Light
• 金额: $ 6.95万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-08 至 2026-05-07
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676501
• 关键词: Ablation; Agonist; Animal Model; Animals; Arrhythmia; Astrocytes; Attention; Behavior; Biological Sciences; Blood flow; Brain; Cardiac; Cardiac Myocytes; Cells; Cellular Morphology; Central Nervous System; Characteristics; Communication; Complex; Development; Educational process of instructing; Enteric Nervous System; Environment; Fertilization; Functional disorder; Future; Gap Junctions; Goals; Growth; Health; Heart; Heart Diseases; Heart Rate; Homeostasis; Human body; Image; Immunohistochemistry; Institution; Kidney; Knock-out; Knowledge; Laboratories; Light; Lung; Mentors; Microscopy; Modeling; Molecular Profiling; Monitor; Morphology; Nervous System Physiology; Nervous System control; Neuroglia; Neurons; Optics; Organ; Organogenesis; Pancreas; Pathology; Pattern; Peripheral; Peripheral Nervous System; Physiological; Physiology; Play; Population; Population Dynamics; Process; Reflex action; Regulation; Research; Resolution; Role; Running; Signal Pathway; Signal Transduction; Skin; Spleen; Stimulus; Structure; System; Technical Expertise; Time; Transgenic Animals; Universities; Ventricular Fibrillation; Work; Zebrafish; calcium indicator; cardiogenesis; cell type; congenital heart disorder; experimental study; heart function; heart rhythm; imaging facilities; in vivo; insight; migration; neural; neural model; neuronal circuitry; neuroregulation; novel; organ growth; response; skills; success; tissue fixing; undergraduate student

Project Summary Organs of the human body rely on complex integration of multiple neuronal circuits in order to maintain homeostasis. For example, the heart must respond to internal and external stimuli and produce sufficient blood flow to meet environmental demands. Glia play critical roles to support nervous system function but are also indispensable for establishment of appropriate circuit structure and physiology. Our lab recently identified a cell type in the heart with many similarities to astroglia populations found elsewhere in the body. This cell type, which we termed cardiac nexus glia, is present as the heart is being formed and is critical for establishment of heart rhythm. Ablation of these glia causes cardiac arrhythmia and ventricular fibrillation, both serious physiological conditions. This project uses the zebrafish animal model to investigate the developmental ontogeny and morphological characteristics of cardiac nexus glia in the developing hearts of living animals (Aim 1). Additionally, it probes the functional relationship between these glia and cardiomyocytes and their roles in modulating heart rate and rhythm (Aim 2). The results of these experiments will contribute crucial detail to our understanding of the multi-faceted roles of glia in the peripheral nervous system and provide important and specific insight about cardiac nexus glia function in heart development and disease. This research will be undertaken in a supportive and collaborative laboratory environment within the Biological Sciences Department at Notre Dame University. It will rely on expertise from staff of the Center for Zebrafish Research and the Integrated Imaging Facility. In addition to the development of bench skills and technical expertise inherent to this project, the applicant will also hone teaching, mentoring, and management skills that will be critical for her future success as a PI running her own research group at a primarily undergraduate institution.

项目摘要 人体器官依赖于多个神经元回路的复杂整合，以维持 体内平衡例如，心脏必须对内部和外部刺激作出反应，并产生足够的血液 以满足环境需求。胶质细胞在支持神经系统功能方面发挥着关键作用，但也 对于建立适当的电路结构和生理学是必不可少的。我们的实验室最近发现了一种细胞 心脏中的星形胶质细胞与身体其他部位的星形胶质细胞有许多相似之处。这种细胞类型， 我们称之为心脏神经胶质细胞，它在心脏形成过程中出现，对心脏的建立至关重要 节奏消融这些神经胶质细胞会导致心律失常和室颤，这两种都是严重的生理性疾病。 条件本研究以斑马鱼为动物模型，研究斑马鱼的发育个体发生， 活体动物心脏发育过程中心脏神经联结胶质细胞的形态学特征（目的1）。此外，本发明还 探讨这些胶质细胞和心肌细胞之间的功能关系及其在心脏调节中的作用。 心率和节律（目标2）。这些实验的结果将有助于我们了解 神经胶质细胞在周围神经系统中的多方面作用，并提供重要和具体的见解， 心脏神经胶质细胞在心脏发育和疾病中的作用。 这项研究将在一个支持和合作的实验室环境中进行， 圣母大学生物科学系。它将依靠中心工作人员的专门知识， 斑马鱼研究和综合成像设施。除了发展板凳技能和 凭借该项目固有的技术专业知识，申请人还将磨练教学、指导和管理 技能，这将是她未来成功的关键，作为一个PI运行她自己的研究小组在一个主要 本科院校。