MAPPING ABNORMAL NEURODEVELOPMENT IN AN ANIMAL MODEL

绘制动物模型中的异常神经发育图

• 批准号: 6969028
• 负责人: LYNN D SELEMON
• 金额: $ 15.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-28 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969028
• 关键词: Macaca; brain injury; brain mapping; brain morphology; developmental disease /disorder; developmental neurobiology; disease /disorder model; early experience; frontal lobe /cortex; hippocampus; histology; longitudinal animal study; magnetic resonance imaging; mental health epidemiology; neurogenesis; postmortem; psychopathology; radiation; schizophrenia; thalamus

The hypothesis that the thalamus is a primary site of pathology in schizophrenia and that thalamic pathology will be tested, as well as consequent pathology in other brain regions, could arise from a prenatal insult. Toward this aim, fetal monkeys have been exposed to x-irradiation in order to substantially reduce thalamic volume and neuron number. During the current grant cycle, the high dimensional brain mapping (HDBM) method developed by and colleagues has been used to assess thalamic volume in fetally irradiated monkeys (FIMs) and has established that fetal irradiation during the time of thalamogenesis produces thalamic pathology in the fully mature macaque that can be detected with neuroimaging techniques. In this grant period, HDBM will be used to examine how other brain regions, specifically the frontal cortex and hippocampus, are affected by early gestational depletion of thalamic neurons and whether the pathology in these regions is comparable to that observed in schizophrenia. The volume and thickness of individual cortical areas, e.g., dorsolateral prefrontal area 46, will be assessed through a novel combination of postmortem histologic and magnetic resonance imaging methodologies. In addition, postmortem analyses of the cytoarchitecture of the hippocampus will probe the cellular basis of alterations in volume and shape of the hippocampus that have been detected via in vivo imaging in FIMs; these analyses may provide insight into the structural underpinnings of similar conformational alterations in schizophrenia patients. Finally, application of the HDBM methodology to a new cohort of FIM and control monkeys at selected developmental intervals will provide a longitudinal picture of the normal development of brain morphology and the interaction of a prenatal lesion on the normal maturational process.

丘脑是精神分裂症和 丘脑病理学将被检查，以及其他大脑区域的导致病理学，可能是由产前侮辱引起的。为了实现这一目标，胎儿猴子已经暴露于X辐射中，以大大减少丘脑的体积和神经元的数量。在当前赠款周期中，由和同事开发的高维大脑图（HDBM）方法已用于评估胎儿辐照的猴子（FIMS）的丘脑体积，并确定在丘脑生成期间，胎儿辐照在丘脑生成期间产生完全的thalamic病理学。可以通过神经影像技术检测到的成熟猕猴。在这一赠款期间，HDBM将用于研究其他大脑区域（特别是额叶皮层和海马）如何受到丘脑神经元的早期妊娠耗竭的影响，以及这些区域中的病理学是否与Schizophrenia中观察到的病理相当。各个皮质区域的体积和厚度，例如背外侧前额叶46，将通过新的后验尸组织学和磁共振成像方法的新组合来评估。此外，海马细胞结构的死后分析将探测通过FIMS中的体内成像检测到的海马体积和形状变化的细胞基础；这些分析可能会深入了解精神分裂症患者类似构象改变的结构基础。最后，在选定的发育间隔内将HDBM方法的应用在新的FIM和对照猴子队中的应用将提供纵向的脑形态发育以及在正常成熟过程中的正常发育以及产前病变的相互作用。