MAPPING ABNORMAL NEURODEVELOPMENT IN AN ANIMAL MODEL OF SCHIZOPHRENIA

绘制精神分裂症动物模型中的异常神经发育图

基本信息

批准号：
7476362
负责人：
LYNN D SELEMON
金额：
$ 28.86万
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：
2007-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7476362
关键词：
Accounting Address Adolescence Adolescent Affect Age Age-Years Anatomy Animal Model Animals Anterior Appendix Area Autopsy Behavioral Brain Brain Mapping Brain imaging Brain region Cell Count Cells Cerebral cortex Clinical Complex Data Data Set Deafferentation procedure Deformity Development Disease Epidemiologic Studies Etiology Exhibits Exposure to Feedback Functional Magnetic Resonance Imaging Functional disorder Funding Genes Genetic Genetic Predisposition to Disease Goals Grant Gray unit of radiation dose Hand Hippocampus (Brain)Histologic Human Image Individual Infection Injury Knowledge Laboratories Lesion Life Link Macaca Magnetic Resonance Imaging Maps Measures Medial Dorsal Nucleus Memory Mental disorders Methodology Methods Metric Modeling Molecular Conformation Monitor Monkeys Morphology Neurologic Neurons Neuropil Neurosciences Neurosciences Research Numbers Pathology Pathology processes Pathway interactions Patients Pattern Performance Perinatal Exposure Phase Phenotype Physiological Prefrontal Cortex Pregnancy Principal Investigator Process Pyramidal Cells Range Relative (related person)Resources Risk Sample Size Scanning Schedule Schizophrenia Secondary to Shapes Short-Term Memory Site Staging Staining method Stains Statistically Significant Stem cells Structure Surface Techniques Technology Testing Thalamic structure Thick Time Tissues Transcend Variant Work abstracting base behavior test brain morphology cingulate cortex cingulate gyrus cohort conformational alteration critical developmental period entorhinal cortex fetal frontal lobe gray matter human data human subject in utero in vivo innovation insight interest irradiation neurodevelopment neurogenesis neuroimaging nonhuman primate novel postnatal prenatal size white matter

项目摘要

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.

丘脑是精神分裂症主要病理部位的假设将测试丘脑病理学以及随后的其他大脑区域的病理学，可能是由产前损伤引起的。为了实现这一目标，胎儿猴接受了 X 射线照射，以大幅减少丘脑体积和神经元数量。在当前的资助周期中，由及其同事开发的高维脑图（HDBM）方法已被用于评估胎儿受辐射猴子（FIM）的丘脑体积，并确定丘脑发生期间的胎儿辐射会在充分的情况下产生丘脑病理学。可以通过神经影像技术检测到的成熟猕猴。在此资助期内，HDBM 将用于检查其他大脑区域，特别是额叶皮层和海马体，如何受到妊娠早期丘脑神经元耗竭的影响，以及这些区域的病理学是否与精神分裂症中观察到的病理学相似。各个皮质区域（例如背外侧前额叶区域 46）的体积和厚度将通过死后组织学和磁共振成像方法的新颖组合进行评估。此外，对海马细胞结构的死后分析将探讨通过 FIM 体内成像检测到的海马体积和形状变化的细胞基础；这些分析可以深入了解精神分裂症患者类似构象改变的结构基础。最后，在选定的发育间隔将 HDBM 方法应用于新的 FIM 和对照猴群，将提供大脑形态正常发育的纵向图景以及产前病变对正常成熟过程的相互作用。