Building Schizophrenia Research in Macedonia

在马其顿建立精神分裂症研究

基本信息

批准号：
8894084
负责人：
ANDREW J DWORK
金额：
$ 38.88万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-18 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8894084
关键词：
Academy Affect Age Aging Arts Autopsy Axon Balkans Benchmarking Biochemical Biological Brain Caliber Cerebrum Collaborations Computer software Core Facility Cortical Contusions Data Data Analyses Disease Dorsal Electron Microscopy Electron Microscopy Facility Elements Equipment Fiber Forensic Medicine Freezing Genetic Genome High-Throughput RNA Sequencing Human Image Analysis Immunohistochemistry Individual Informatics Internet Ions Knowledge Label Laboratories Lead Learning Left Liquid Chromatography Macedonia Major Depressive Disorder Mass Spectrum Analysis Measurement Measures Mentors Mentorship Messenger RNA Methodology Methods Microglia Molecular Profiling Myelin Myelin Sheath Neurons New York Oligodendroglia Optic Nerve Optic tract structure Outcome Participant Pathologist Peptides Population Process Protein Chemistry Proteins Proteomics Psychological reinforcement RNA Sequence Analysis RNA Sequences Reporting Research Research Personnel Research Training Resources Role Sampling Schizophrenia Science Scientist Sensory Shotguns Structural defect Students Supervision System Techniques Teleconferences Testing Thick Tissues Training Universities Visit age effect age related comparative computerized data processing density design experience innovation instrument instrumentation light microscopy mRNA Expression normal aging novel pressure professor sex transcriptome sequencing white matter

项目摘要

DESCRIPTION (provided by applicant): We propose a collaboration between Columbia University, in New York, and the Macedonian Academy of Sciences and Arts, in Skopje, to investigate abnormalities of cerebral white matter, and particularly myelin, in schizophrenia. The preludes to this project are a successful collaboration to collect autopsy brains in Macedonia for research on schizophrenia, a successful collaboration to establish electron microscopy in Macedonia for the study of schizophrenia, and a longstanding conviction, continually receiving reinforcement, that subtle abnormalities of myelin are important in schizophrenia. The project consists of 4 elements, each designed to advance our knowledge of schizophrenia, the training of Macedonian scientists, and an important, sustainable scientific capability in Macedonia. First, we propose to use electron microscopy to measure the sizes of axons and their myelin sheaths in the white matter, in order to determine whether these are abnormal in schizophrenia, and whether age-related changes are different in people with and without schizophrenia. This will involve aspiring Macedonian scientists in schizophrenia research and will solidify the role of our electron microscopy facility as a national resource. Second, we propose to use stereology to determine densities of oligodendrocytes and microglia in white matter. This will be a novel use of stereology, which generally shuns the measurement of densities because of unknown changes in tissue volumes, but these difficulties can be overcome. It is not clearly known what changes in the cellular composition of white matter take place in schizophrenia or in normal aging. We are already training a Macedonian forensic pathologist in stereology, and the project will support a facility in which he can train others. Third, we and others have strong evidence for abnormal levels of certain myelin-related proteins or their mRNA in schizophrenia, but in general, only the most abundant proteins have been investigated. Proteomic techniques exist that can measure essentially all proteins in a piece of tissue simultaneously. We will bring a Macedonian scientist to begin to analyze samples while learning to use state-of-the-art label-free proteomics in the core facility at Columbia, after which the Ministry of Science in Macedonia will support the purchase of similar instrumentation to establish a world-class facility in the Macedonia, where analysis will continue, with continued collaborative support from the director of the facility at Columbia. Fourth, we will bring a Macedonian expert in informatics to the Columbia genome facility, where he will learn to process raw data from high-throughput RNA sequencing (RNA-seq) that will elucidate levels of essentially all mRNA species in our samples, and he will train students in Macedonia in these methods, which have wide biological applicability. The final outcome should be a major role for Macedonia in solving a difficult and important problem, and at least four core facilities for research and training.

描述（由申请人提供）：我们建议纽约哥伦比亚大学和斯科普里马其顿科学与艺术学院合作，研究精神分裂症中脑白质，特别是髓磷脂的异常。该项目的前奏是在马其顿成功合作收集尸检大脑以研究精神分裂症，在马其顿成功合作建立电子显微镜以研究精神分裂症，以及长期以来不断得到强化的信念，即髓磷脂的细微异常是对精神分裂症很重要。该项目由 4 个要素组成，每个要素都旨在增进我们对精神分裂症的了解、培训马其顿科学家以及培养马其顿重要的、可持续的科学能力。首先，我们建议使用电子显微镜测量白质中轴突及其髓鞘的大小，以确定这些在精神分裂症患者中是否异常，以及精神分裂症患者和非精神分裂症患者与年龄相关的变化是否不同。这将吸引有抱负的马其顿科学家参与精神分裂症研究，并将巩固我们的电子显微镜设施作为国家资源的作用。其次，我们建议使用体视学来确定白质中少突胶质细胞和小胶质细胞的密度。这将是体视学的一种新颖用途，由于组织体积的未知变化，体视学通常避免测量密度，但这些困难是可以克服的。目前尚不清楚精神分裂症或正常衰老过程中白质细胞组成发生了什么变化。我们已经在体视学方面培训一名马其顿法医病理学家，该项目将支持一个设施，供他培训其他人。第三，我们和其他人有强有力的证据精神分裂症中某些髓磷脂相关蛋白或其 mRNA 的异常水平，但一般来说，只研究了最丰富的蛋白质。蛋白质组学技术基本上可以同时测量一块组织中的所有蛋白质。我们将带一名马其顿科学家开始分析样本，同时在哥伦比亚的核心设施中学习使用最先进的无标记蛋白质组学，之后马其顿科学部将支持购买类似的仪器来建立马其顿的一个世界级设施，在哥伦比亚设施主任的持续合作支持下，分析将继续进行。第四，我们将带一位马其顿信息学专家到哥伦比亚基因组设施，在那里他将学习处理来自高通量 RNA 测序 (RNA-seq) 的原始数据，这将阐明我们样本中基本上所有 mRNA 种类的水平，他将为马其顿的学生提供这些具有广泛生物学适用性的方法的培训。最终结果应该是马其顿在解决一个困难而重要的问题方面发挥主要作用，并至少有四个核心研究和培训设施。