ShEEP Request for Confocal Microscope System

ShEEP 请求共焦显微镜系统

• 批准号: 9794913
• 负责人: Bruce A. Citron
• 金额: --
• 依托单位: VA NEW JERSEY HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794913
• 关键词: Acute; Affect; Alzheimer' s Disease; Americas; Antioxidants; Anxiety; Area; Bacterial Infections; Behavior; Bile Acids; Bile fluid; Brain Stem; Cell physiology; Cells; Chemical Exposure; Cholestasis; Chronic; Collection; Color; Computer software; Dementia; Demyelinating Diseases; Diet; Dimensions; Disease; Evaluation; Exposure to; Fluorescein-5-isothiocyanate; GRM1 gene; Glucose; Glutamine; Gulf War; Health; Hippocampus (Brain); Hour; Image; Immunohistochemistry; Impulsivity; International; Investigation; Lasers; Light; Liver Regeneration; Liver diseases; Location; Malignant Neoplasms; Manufacturer Name; Measures; Metabolism; Metals; Methods; Microscope; Microscopy; Modeling; Morphology; Multiple Sclerosis; Nerve Degeneration; Neurons; Oils; Opioid; Organelles; Parkinson Disease; Pathologic; Peptides; Phase; Positioning Attribute; Predisposition; Production; Psychological reinforcement; Reproducibility; Research; Research Personnel; Resolution; Role; Scanning; Semiconductors; Services; Shapes; Sheep; Side; Slide; Source; Speed; Synaptic plasticity; System; Therapeutic; Therapeutic Agents; Tissues; Total Parenteral Nutrition; Traumatic Brain Injury; Ultrasonics; Veterans; Weight; brain behavior; chronic traumatic encephalopathy; cyanine dye 5; detector; experience; fluorescence microscope; functional loss; hypocretin; immunocytochemistry; improved; improved outcome; instrument; lens; melanoma; mild traumatic brain injury; mouse model; neuroinflammation; novel; opioid use; photomultiplier; population health; prevent; repaired; research and development; side effect; therapy design; tool; toxic metal; two-dimensional; volatile organic compound

The VANJHCS researchers have a great deal of experience investigating the underlying mechanisms and treatments for a variety of disorders afflicting Veterans. Tools have included fluorescent microscopes for immunohistochemistry and immunocytochemistry to determine the locations and changes in important cellular factors. The problem is that essential pathological and restorative mechanisms involve morphological shapes, colocalizations, subcellular associations, etc., unattainable in two dimensions and this is limiting our abilities. To obtain a three dimensional picture of what is really happening with respect to tissues, cells, and organelles, while we search for optimal therapeutic strategies for Veterans, a laser scanning confocal microscope is required. Our facility does not have a confocal capability, although several of our investigators have taken advantage of these systems at previous stations in the past. The instrument sought would excite with lasers for probes in the blue, green, red, and infrared ranges. Emissions, spectrally scanned, would be measured with photomultiplier plus higher sensitivity semiconductor detectors. A motorized stage will enable reproducible positioning and automated collection of multiple fields. Capturing involves a galvanometer driven or a resonance, high speed scanner. Our objectives will include a wide field as well as a high resolution, 1.4 N.A. 60 X oil lens. Some of the specific projects that will be aided by the confocal include Dr. Citron's studies of chronic TBI (Preventing TBI-Induced Chronic Functional Loss with a Neuroprotective Antioxidant) and also Gulf War Veteran's neurodegeneration (Neurodegenerative changes after exposure to Gulf War insults), Dr. Beck's studies of Gulf War Veteran's Illnesses (Neuroinflammation and abnormal behavior following combined chemical exposures and bacterial infection), Parkinson's disease (Volatile organic compound effects on brain and behavior), glucose-inhibited neurons (Role of glucose-inhibited orexin neurons in weight regain following dieting), and also opioid use (Determining the relationship between opioid use and avoidance susceptibility), Dr. Chen's research with melanomas (GRM1-induced HIF-1α and reprogramming of glutamine metabolisms in melanoma), Dr. Dowling’s investigations of dementia and neurodegeneration (Novel EPO peptide therapy for a new mouse model of dementia), demyelinating disease (EPO fragments for demyelinating disease treatment), multiple sclerosis, and brain trauma (Short stabilized EPO-peptide as side-effect free therapeutic agents for multiple sclerosis and acute brain trauma), Dr. Pang's evaluation of opioid effects on synaptic plasticity (Hippocampus, synaptic plasticity and anxiety vulnerability) and his studies of traumatic brain injury (mTBI and brainstem modulatory systems: Implications for impulsivity and reinforcement), Dr. Guo's examinations of bile production (Gut bile acids, Fxr, & Fgf15 in total parenteral nutrition-associated cholestasis) and also of liver disease (Role of FGF15 in liver regeneration). The collective experience within our Research & Development service indicates that our very collaborative group would make excellent use of the three dimensional resolution and quantitative capacities provided by a confocal system to best advance our research.

VANJHCS的研究人员在调查潜在的 困扰退伍军人的各种疾病的机制和治疗。工具有 包括免疫组织化学和免疫细胞化学的荧光显微镜 以确定重要细胞因子的位置和变化。问题是， 基本的病理和修复机制涉及形态形状， 共定位、亚细胞联合等，在两个维度上是无法实现的，这是 限制我们的能力。为了获得真实情况的三维图像 关于组织、细胞和细胞器，在我们寻找最佳治疗方法的同时 对于退伍军人战略，需要一台激光扫描共聚焦显微镜。我们的设施 没有共焦能力，尽管我们的几名调查人员已经采取了 过去这些系统在以前的车站的优势。所寻求的工具将是 用激光激发蓝色、绿色、红色和红外范围内的探测器。排放， 光谱扫描，将使用光电倍增管和更高的灵敏度进行测量 半导体探测器。电动平台将实现可重现的定位和 自动收集多个字段。捕获涉及振镜驱动或 共振，高速扫描仪。我们的目标将包括广泛的领域和高度 分辨率，1.4 N.A.60 X油性镜头。一些具体的项目将得到 Conocus包括Citron博士对慢性脑损伤(预防脑损伤诱导的慢性)的研究 使用神经保护性抗氧化剂造成的功能损失)，以及海湾战争退伍军人的 神经退行性变(暴露于海湾战争侮辱后的神经退行性变化)，Dr。 贝克对海湾战争退伍军人疾病(神经炎症和异常)的研究 联合接触化学物质和细菌感染后的行为)，帕金森病 疾病(挥发性有机化合物对大脑和行为的影响)，葡萄糖抑制 神经元(葡萄糖抑制的食欲素神经元在节食后体重恢复中的作用)，以及 也是阿片类药物的使用(确定阿片类药物的使用和避免之间的关系 易感性)，陈博士对黑色素瘤的研究(GRM1诱导的HIF-1α和 黑色素瘤中谷氨酰胺代谢的重新编程)，道林博士对 痴呆和神经退行性变(新的EPO肽疗法用于新的小鼠模型 痴呆)、脱髓鞘疾病(用于脱髓鞘疾病治疗的EPO片段)、 多发性硬化症和脑损伤(无副作用的稳定EPO短肽 多发性硬化症和急性脑损伤的治疗药物)，彭博士的评估 阿片类药物对突触可塑性(海马体、突触可塑性和焦虑)的影响 脆弱性)和他对创伤性脑损伤(mTBI和脑干调制)的研究 系统：冲动和强化的含义)，郭博士对胆汁的检查 生产(全肠外营养相关的肠道胆汁酸、FXR和Fgf15 胆汁淤积症)和肝病(FGF15在肝脏再生中的作用)。集体 我们研发服务的经验表明，我们非常 协作小组将出色地利用三维分辨率和 由共焦系统提供的量化能力，以最好地推动我们的研究。