SYNAPTIC ALTERATIONS AFTER HYPOGLYCEMIC SEIZURES

低血糖癫痫发作后的突触改变

基本信息

批准号：
7500167
负责人：
KELVIN A YAMADA
金额：
$ 18.62万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7500167
关键词：
4-Aminopyridine Abbreviations Ablation Acute Adverse effects Affect Animal Model Animals Atmospheric Pressure Brain Carbon Dioxide Cell Death Cephalic Cerebrospinal Fluid Cessation of life Child Clinical Research Complication Complications of Diabetes Mellitus Craniotomy Dendrites Dendritic Spines Diabetes Mellitus Focal Seizure Functional disorder Glucose Green Fluorescent Proteins Histologic Hour Human Hypoglycemia Hypoglycemic Agents Image Impaired cognition Incidence Individual Injury Insulin Insulin-Dependent Diabetes Mellitus Intervention Laser Surgery Lasers Lead Link Manuals Metabolic Methods Microscopy Modeling Monitor Morphology Mus Nerve Degeneration Neurologic Neuronal Dysfunction Neuronal Injury Neurons Numbers Operative Surgical Procedures Patients Phase Physiologic pulse Prevalence Proteins Public Health Pulse taking Reaction Recovery Research Research Design Rodent Role Seizures Structure Synapses Techniques Testing Tissues Transgenic Mice Water Week abstracting bone cranium day diabetic in vivo novel prevent prospective research study soft tissue two-photon type I diabetic

项目摘要

Abstract Synaptic alterations after hypoglycemic seizures The independent roles of hypoglycemia and seizure activity in producing neurological deficits and cognitive impairment in children with insulin-dependent (Type I) diabetes are not completely understood. The studies proposed will test the hypothesis that the combined insult of brain glucopenia with the added metabolic demand of seizures produces increased neuronal death, but also structural synaptic alterations that underlie neuronal dysfunction in the absence of cell death. The objective of this project is to develop in vivo imaging methods to detect and observe serial changes in dendritic spines of cortical neurons following hypoglycemia combined with seizures, to evaluate whether there are synergistic injurious effects. To examine these issues, creation of a cranial window with a novel laser surgery technique combined with two-photon microscopy will enable in vivo imaging of dendritic structures in YFP expressing cortical neurons serially monitored at baseline and during hypoglycemia without and with focal seizures produced by 4-aminopyridine (4-AP). RELEVANCE TO PUBLIC HEALTH: Serial neuronal imaging of synaptic structures in vivo, using an animal model of hypoglycemia combined with seizures in rodents will enable studies relevant to understanding the causes and mechanisms of synaptic structural alterations and dysfunction due to hypoglycemia, seizures, and diabetes in diabetic humans. The imaging method proposed will greatly enhance a variety of studies that employ serial imaging using the cranial window technique with multiphoton microscopy. Understanding mechanisms of diabetes/diabetes complication-induced brain dysfunction may lead to new targets for treatment interventions to prevent or retard cognitive impairment in diabetes. RELEVANCE TO PUBLIC HEALTH: Serial neuronal imaging of synaptic structures in vivo, using an animal model of hypoglycemia combined with seizures in rodents will enable studies relevant to understanding the causes and mechanisms of synaptic structural alterations and dysfunction due to hypoglycemia, seizures, and diabetes in diabetic humans. The imaging method proposed will greatly enhance a variety of studies that employ serial imaging using the cranial window technique with multiphoton microscopy. Understanding mechanisms of diabetes/diabetes complication-induced brain dysfunction may lead to new targets for treatment interventions to prevent or retard cognitive impairment in diabetes.

抽象的低血糖癫痫发作后的突触改变低血糖和癫痫发作在产生神经缺陷和认知方面的独立作用胰岛素依赖型（I 型）糖尿病儿童的损伤尚不完全清楚。研究提议将检验以下假设：脑葡萄糖减少症与增加的代谢相结合的损害癫痫发作的需求会导致神经元死亡增加，但也会导致突触结构改变在没有细胞死亡的情况下，神经元功能障碍。该项目的目标是开发体内成像检测和观察低血糖后皮质神经元树突棘系列变化的方法结合癫痫发作，评估是否存在协同损害作用。为了考察这些问题，利用新型激光手术技术结合双光子显微镜创建颅窗将能够对表达 YFP 的皮层神经元的树突结构进行体内成像，并在基线上进行连续监测以及在没有或有 4-氨基吡啶 (4-AP) 引起的局灶性癫痫发作的低血糖期间。与公众健康的相关性：使用动物对体内突触结构进行连续神经元成像啮齿类动物的低血糖和癫痫发作模型将使相关研究能够了解低血糖、癫痫和癫痫引起的突触结构改变和功能障碍的原因和机制糖尿病人的糖尿病。所提出的成像方法将极大地增强各种研究使用颅窗技术和多光子显微镜进行串行成像。理解糖尿病/糖尿病并发症引起的脑功能障碍的机制可能会带来新的治疗目标预防或延缓糖尿病认知障碍的干预措施。与公众健康的相关性：使用动物对体内突触结构进行连续神经元成像啮齿类动物的低血糖和癫痫发作模型将使相关研究能够了解低血糖、癫痫和癫痫引起的突触结构改变和功能障碍的原因和机制糖尿病人的糖尿病。所提出的成像方法将极大地增强各种研究使用颅窗技术和多光子显微镜进行串行成像。理解糖尿病/糖尿病并发症引起的脑功能障碍的机制可能会导致新的目标预防或延缓糖尿病认知障碍的治疗干预措施。