Coupling regional brain tissues with tissue chips

将区域脑组织与组织芯片耦合

基本信息

批准号：
10631165
负责人：
Larry J. Millet
金额：
$ 7.65万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10631165
关键词：
ANXA5 gene Agonist Alcoholism Anatomy Animal Model Animals Award Axon Behavior Biological Assay Biological Process Brain Brain region Cardiovascular system Cell Nucleus Cells Cerebrospinal Fluid Clinical Trials Coculture Techniques Communication Complex Coupling Cues Dense Core Vesicle Diabetes Mellitus Drug Modulation Drug Targeting Event Fluorescence Microscopy Goals Health Hippocampus Human Hypothalamic structure Image Immune In Vitro Individual Intervention Intranasal Administration Knowledge Location Marketing Measures Mental Depression Mental disorders Metabolic Metabolic Diseases Microfluidics Microglia Microscopy Midbrain structure Modeling Molecular Molecular Conformation Nerve Degeneration Neurobiology Neurodegenerative Disorders Neurons Neurosciences Research Neurosecretory Systems Neurosphere Nucleus Accumbens Organ Model Outcome Oxytocin PHluorin Pathway interactions Pattern Pharmaceutical Preparations Physiological Propidium Diiodide Psychiatric therapeutic procedure Rat Transgene Rattus Recombinant adeno-associated virus (rAAV)Regulation Resolution Signal Transduction Slice Small Business Technology Transfer Research Source Surface Synapses System Testing Thalamic structure Therapeutic Tissue Microarray Tissue imaging Tissues Vasopressins Ventral Striatum Vesicle Viral Work autism spectrum disorder axon growth brain based brain tissue circadian circadian pacemaker drug candidate drug testing fluorophore high resolution imaging imaging study immunoregulation improved in vivo in vivo imaging interstitial magnocellular melanocortin receptor migration miniaturize nanoscale nervous system disorder neurogenesis organ on a chip pharmacologic post-traumatic stress pre-clinical preclinical study presynaptic social social cognition theories therapeutic target tissue culture tissue fixing tissue preparation tool translational neuroscience vesicular release

项目摘要

Project Summary The hypothalamus is the master regulator of the neuroendocrine system, it synapses to multiple brain regions and coordinates physiological functions of the body. Magnocellular neurons (MCN) are key producers of oxytocin and vasopressin, they regulate neuroendocrine functions and differentially secrete oxytocin into the brain, the cerebrospinal fluid, and the circulatory system. How MCN differentially regulate oxytocin release remains unresolved. Oxytocin is involved in and studied as a candidate treatment for psychiatric and metabolic conditions such as autism, depression, and post-traumatic stress. Miniaturized models of organs and tissues are indispensable tools for bridging the gap between preclinical animal models and clinical trials. Human and animal microfluidic tissue-chips provide unparalleled control and access to cells and tissues where anatomical and technical barriers preclude in vivo studies. We will create a microfluidic-based brain tissue chip for coupling brain slices and primary neurospheres from at least two regions of the brain. Surface-patterned guidance cues will be used to direct the growth of axons from oxytocinergic magnocellular neurons toward target brain tissues. Our microfluidic system will allow for brain-to-synapse connections for the direct observation of nano-scale oxytocin vesicles to achieve detailed studies of how different drugs influence the locations and dynamics of oxytocin vesicle release. More generally, potential applications of our brain-to-brain tissue culture system could include the ability to connect multiple brain regions in vitro for the benefit of immune regulation studies, neuroendocrine regulation studies, neurogenesis and migration studies, and how drugs influence molecular and cellular dynamics.

项目摘要下丘脑是神经内分泌系统的主要调节剂，它突触到多个大脑区域和协调身体的生理功能。巨细胞神经元（MCN）是关键催产素和加压素的产生者，它们调节神经内分泌功能并差异分泌催产素进入大脑，脑脊液和循环系统。 MCN如何差异调节的催产素释放尚未解决。催产素参与并作为候选治疗研究对于自闭症，抑郁症和创伤后压力等精神病和代谢状况。器官和组织的微型模型是必不可少的工具，用于弥合差距临床前动物模型和临床试验。人类和动物微流体组织芯片提供无与伦比的控制和进入细胞和组织，其中解剖和技术障碍在体内排除研究。我们将创建一个基于微流体的脑组织芯片，用于耦合大脑切片和主要来自至少两个大脑区域的神经球。表面图案的指导提示将用于指导从催产素能细胞神经元向靶向脑组织的轴突生长。我们的微流体系统将允许直接观察纳米级催产素的脑之间连接囊泡以实现不同药物如何影响催产素的位置和动力学的详细研究囊泡释放。更一般地，我们的大脑到脑组织培养系统的潜在应用可能包括能够在体外连接多个大脑区域以获取免疫调节研究的能力，神经内分泌调节研究，神经发生和迁移研究以及药物如何影响分子和细胞动力学。