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的研究人员有大量的经验调查的基础 机制和治疗各种疾病折磨退伍军人。工具 包括荧光显微镜免疫组织化学和免疫细胞化学 以确定重要细胞因子的位置和变化。问题是 基本的病理学和恢复机制涉及形态学形状， 共定位、亚细胞关联等，在二维空间中是无法实现的， 限制了我们的能力为了获得真实发生的三维图像 在我们寻找最佳治疗方法的同时， 为退伍军人的战略，激光扫描共聚焦显微镜是必需的。我们的设施 没有共焦能力，尽管我们的几个研究人员已经采取了 这些系统在以前的车站的优势。所寻求的文书将 在蓝色、绿色、红色和红外范围内用激光激发探针。排放， 光谱扫描，将测量光电倍增管加上更高的灵敏度 半导体探测器电动载物台将实现可再现的定位， 自动收集多个字段。捕获涉及电流计驱动或 共振，高速扫描仪。我们的目标将包括广泛的领域以及高 分辨率，1.4 60倍油透镜。一些具体项目将得到援助， 共聚焦包括Citron博士对慢性TBI（预防TBI诱导的慢性TBI）的研究 神经保护性抗氧化剂的功能丧失）以及海湾战争退伍军人的 神经变性（海湾战争后的神经变性变化），博士。 贝克对海湾战争退伍军人疾病的研究（神经炎症和异常 化学暴露和细菌感染后的行为），帕金森氏症 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（葡萄糖抑制食欲素神经元在节食后体重恢复中的作用），以及 阿片类药物使用（确定阿片类药物使用和避免之间的关系） 易感性），陈博士对黑色素瘤的研究（GRM 1诱导的HIF-1α和 重编程的谷氨酰胺代谢在黑色素瘤），道林博士的调查， 痴呆和神经退行性变（用于痴呆和神经退行性变的新小鼠模型的新型EPO肽疗法） 痴呆），脱髓鞘疾病（用于脱髓鞘疾病治疗的EPO片段）， 多发性硬化症和脑外伤（短稳定的EPO-肽作为无副作用 多发性硬化症和急性脑外伤的治疗药物），彭博士的评价 阿片类药物对突触可塑性的影响（海马，突触可塑性和焦虑） 脆弱性）和他对创伤性脑损伤（mTBI和脑干调节 系统：冲动和强化的含义），郭博士的胆汁检查 生产（肠道胆汁酸，Fxr，和Fgf 15在全胃肠外营养相关 胆汁淤积）以及肝脏疾病（FGF 15在肝再生中的作用）。集体 我们的研发服务经验表明， 协作组将充分利用三维分辨率， 共聚焦系统提供的定量能力，以最好地推进我们的研究。