Golgi Studies of Schizophrenia

精神分裂症的高尔基体研究

基本信息

批准号：
8073056
负责人：
ANDREW J DWORK
金额：
$ 50.73万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8073056
关键词：
Administrative Supplement Affect Age Amygdaloid structure Animal Model Apical Atrophic Autopsy Brain Brain region Cells Clinical Cognitive deficits Collection Cytoskeletal Proteins Data Dendrites Dendritic Spines Diffusion weighted imaging Dorsal Forensic Medicine Fresh Tissue Functional disorder Funding Glutamates Golgi Apparatus Golgi method Grant Hippocampal Formation Hippocampus (Brain)Horns Human Institutes Institution Laboratories Lead Left MFGE8 gene Macedonia Macedonia (Republic)Medial Medial Dorsal Nucleus Mental disorders Methods Microtubule-Associated Protein 2 Midbrain structure Modification Morphology Neurobiology Neurons Pattern Population Prefrontal Cortex Procedures Process Pyramidal Cells Random Allocation Reporting Sampling Schizophrenia Site Slide Specimen Staining method Stains Stress Structure Techniques Thalamic structure Tissue Banks Tissues Toxicology United States National Institutes of Health Vertebral column brain tissue cholinergic density dentate gyrus hippocampal pyramidal neuron human tissue immunoreactivity improved in vivo lateral ventricle neurogenesis neuronal cell body neuropathology prospective psychologic public health relevance sex success tissue fixing white matter

项目摘要

DESCRIPTION (provided by applicant): Golgi staining reveals the anatomical structure of dendrites. While Golgi methods have yielded some of the most robust histological findings in schizophrenia, studies that use these techniques are uncommon, probably because the techniques have been difficult to apply and notoriously capricious. We have developed a new modification of the Golgi-Cox method that has yielded unprecedented reliability, with consistent staining in over 100 consecutive blocks from over 70 consecutive autopsy cases. There is a uniform distribution of stained neurons that allows systematic random sampling of neurons for analysis. We propose to use this material to study dendritic arborization and spine density in 20 schizophrenia subjects matched by age and sex to 40 subjects without psychiatric disease, all evaluated clinically by psychological autopsy. We will analyze dendritic arborization and spine density in dorsal (BA9) and ventral (BA45) prefrontal cortex, and in the hippocampal formation (subiculum, CA3, CA1, and dentate gyrus). Since every section cut from a block is stained well, we propose to share the slides with other laboratories that wish to perform additional analyses. This application also includes continuation of our ongoing collection of brain specimens and psychological autopsies in the Republic of Macedonia. This collection provides the fresh tissue for our Golgi studies and for many other studies of the neurobiology of psychiatric illnesses, both in our department and at other institutions. The specimens and data are stored in our department and subjected to rigorous clinical, neuropathological, and toxicological review. PUBLIC HEALTH RELEVANCE: Schizophrenia is a devastating illness that affects 1% of the population. The structural abnormalities of the brain that underlie schizophrenia are poorly understood, but they are likely to involve the dendritic processes that extend outwards from neurons. We have developed improved procedures to visualize these processes in human brain tissue from autopsies, and we will use these methods to determine whether there are consistent abnormalities of brain structure in schizophrenia.

描述（由申请人提供）：高尔基体染色揭示了树突的解剖结构。虽然高尔基方法在精神分裂症方面取得了一些最可靠的组织学发现，但使用这些技术的研究并不常见，可能是因为这些技术难以应用且反复无常。我们开发了一种新的高尔基-考克斯方法，该方法具有前所未有的可靠性，对 70 多个连续尸检病例的 100 多个连续块进行了一致的染色。染色神经元呈均匀分布，允许对神经元进行系统随机采样以进行分析。我们建议使用这种材料来研究 20 名精神分裂症受试者（年龄和性别与 40 名无精神疾病受试者相匹配）的树突分枝和树突棘密度，所有受试者均通过心理尸检进行临床评估。我们将分析背侧 (BA9) 和腹侧 (BA45) 前额皮质以及海马结构（下下层、CA3、CA1 和齿状回）的树突分枝和棘密度。由于从块上切下的每个切片都染色良好，我们建议与希望进行额外分析的其他实验室共享幻灯片。该应用程序还包括继续我们在马其顿共和国正在进行的脑标本收集和心理尸检。该集合为我们的高尔基体研究以及我们部门和其他机构的许多其他精神疾病神经生物学研究提供了新鲜组织。标本和数据存储在我们的部门，并经过严格的临床、神经病理学和毒理学审查。公共卫生相关性：精神分裂症是一种毁灭性的疾病，影响着 1% 的人口。人们对精神分裂症背后的大脑结构异常知之甚少，但它们很可能涉及从神经元向外延伸的树突状过程。我们已经开发出改进的程序，可以从尸检中可视化人类脑组织中的这些过程，我们将使用这些方法来确定精神分裂症患者的大脑结构是否存在一致的异常。