Oligodendrocytes and neuron pathology in cingulate cortex

扣带皮层少突胶质细胞和神经元病理学

基本信息

批准号：
8080383
负责人：
PATRICK R HOF
金额：
$ 23.2万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8080383
关键词：
2&apos ,3&apos -Cyclic-Nucleotide Phosphodiesterases Address Affect Anisotropy Anterior Architecture Attention Autopsy Behavior Behavioral Brain Brain imaging Cell Count Cellular Morphology Characteristics Clinical Data Demyelinating Diseases Dendritic Spines Development Diffusion Magnetic Resonance Imaging Disease Fluorescent Dyes Functional Imaging Functional disorder Funding Gene Mutation Gene Proteins Genes Gray unit of radiation dose Human Image Image Analysis Investigation Knockout Mice Label Lead Limbic System Link Magnetic Resonance Magnetism Measures Medial Memory Methods Microscopy Modeling Modification Molecular Morphology Motivation Mus Mutant Strains Mice Mutation Myelin Neurons Oligodendroglia Outcome Pathogenesis Pathology Pathway interactions Patients Pattern Phenotype Play Postmortem Changes Prefrontal Cortex Procedures Pyramidal Cells Quaking Mice Quantitative Microscopy Relative (related person)Resolution Role Schizophrenia Spatial Distribution Specimen Techniques Time Time Study Vertebral column base cingulate cortex density design dysmyelination endophenotype gene gun hippocampal pyramidal neuron in vivo indexing mouse model myelination neuropathology programs protein expression white matter

项目摘要

Project 1. Project 1. An investigation of oligodendroglia in schizophrenia. Demyelinating diseases have been known to be associated with behavioral changes. Recently, the expression levels of several myelin-related genes have been shown to be consistently decreased in postmortem schizophrenic brains compared to controls. Magnetic transfer imaging (MTI) has also shown consistent reduction in myelin content in schizophrenic brains. Diffusion tensor imaging (DTI), which measures the directionality of white matter tracts, has shown a decrease in anisotropy in the brains of schizophrenic patients, suggesting disruptions in white matter tract coherence and directionality in this disease. These data together make a strong case for oligodendrocyte dysfunction in schizophrenia. The anterior cingulate cortex plays a significant role in motivation, attention, and behavior and, as a component of the limbic system, in affect and memory. It has been clearly implicated in schizophrenia by studies of cytoarchitectural postmortem changes and functional imaging showing hypometabolism in this region in schizophrenia. In this project, we propose a quantitative analysis of possible relationships between oligodendrocytic pathology and abnormalities in cytoarchitecture in the cingulate cortex of postmortem brains from schizophrenic patients and neuropathologic and brain imaging analyses of relevant mice mutants such as the Quaking mouse, as well as genetically modified mice such as MAG, RPTPfi, CNPase, or MAGI knock-outs. Our analyses will use advanced microscopy quantitative approaches including the most rigorous stereologic methods for cell counting, estimators of spatial cellular distribution and cytoarchitectural boundaries, as well as single cell morphology by intracellular loading of fluorescent dyes or gene-gun-based DiOlistics techniques. We also are assessing progression of potential changes in white matter integrity using high field magnetic resonance microscopy in vivo at 9.4 T in the relevant mouse models. The combined analysis of human specimens and relevant mice models within the context of this program offers a superb opportunity to investigate myelin deficits that have a clinical impact and to determine the molecular, developmental, and morphologic characteristics of the neuronal circuits whose alteration is likely to underlie the pathogenesis and clinical manifestations of schizophrenia. the molecular, developmental, and morphologic characteristics of the neuronal circuits whose alteration is likely to underlie the pathogenesis and clinical manifestations of schizophrenia.

项目1。项目1。对精神分裂症中的寡聚胶质素的调查。脱髓鞘疾病已经已知与行为变化有关。最近，几种髓磷脂相关的表达水平与之相比控件。磁转移成像（MTI）也显示出髓磷脂含量一致的降低精神分裂的大脑。扩散张量成像（DTI），它测量了白质区的方向性，精神分裂症患者大脑的各向异性显示出降低，表明白色干扰物质道的连贯性和该疾病的方向性。这些数据共同为精神分裂症中的少突胶质细胞功能障碍。前扣带回皮层在动机，注意力和行为，以及作为边缘系统的组成部分，在情感和记忆中。它有通过研究细胞结构后变化和功能性的研究明显与精神分裂症有关成像显示精神分裂症该地区的缺乏代谢。在这个项目中，我们提出了一个定量分析细胞结构中的少突胶质病理学与异常之间的关系在精神分裂症患者以及神经病理学和脑的尸体大脑的扣带皮层中相关小鼠突变体（例如Quaking House）以及转基因小鼠的成像分析例如MAG，RPTPFI，CNPase或MAGI淘汰赛。我们的分析将使用高级显微镜定量方法，包括用于细胞计数的最严格的立体方法，估计值空间细胞分布和细胞结构边界以及细胞内单细胞形态荧光染料或基因基因二元学技术的加载。我们还在评估使用高场磁共振显微镜在体内9.4 t的潜在变化相关的鼠标模型。人类标本和相关小鼠模型的组合分析该程序的背景提供了一个极好的机会来调查具有临床的髓鞘缺损影响并确定神经元的分子，发育和形态特征改变的电路可能是精神分裂症的发病机理和临床表现的基础。改变的神经元回路的分子，发育和形态特征可能是精神分裂症的发病机理和临床表现的基础。