Golgi Studies of Schizophrenia

精神分裂症的高尔基体研究

• 批准号: 6922897
• 负责人: ANDREW J DWORK
• 金额: $ 40.03万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922897
• 关键词: brain mapping; dendrites; hippocampus; human subject; human tissue; pathologic process; prefrontal lobe /cortex; pyramidal cells; schizophrenia; silver impregnation; visual cortex

DESCRIPTION: (provided by applicant) In a previous study, we found a profound loss of spines on the apical dendrites of pyramidal neurons in the left subiculum of individuals with schizophrenia, with no overlap between subjects with schizophrenia and those without psychiatric illness. In addition, there was a significant reduction in the apical dertdritic arbors of these cells, but not in their basilar dendritic arbors, nor in the dendritic arbors of pyramidal neurons in the adjacent neocortex. Since completing that study, we have improved our technique for rapid Golgi staining, so that it is now applicable to tissue from the pre-neuroleptic era, that has been in lormalin for over 50 years. Furthermore, the number of Golgi-impregnated neurons is now sufficient to permit random sampling of neurons for evaluation. Similar findings by other researchers who examined other regions of the brain, and our own data showing abnormalities of subicular MAP2, supporting diminished cognitive reserve, and documenting the longitudinal course of cognitive and clinical deterioration, all support the notion of decreased synaptic connectivity as a substrate for schizophrenia. We now propose to employ improved Golgi staining to study 5 groups of 20 individuals in order: (1) To evaluate the replicability of our previous finding. (2) To determine whether similar abnormalities are present in archived brains from schizophrenia patients who died before the introduction of neuroleptic drugs. It is possible that these drugs induce the loss of spines, that they protect against it, or that they do neither. (3) To determine whether similar abnormalities are present in the brains of young schizoprhenia subjects, which will help to determine whether the loss of spines is more likely a cause or a result of schizophrenia, and whether it is progressive. (4) To evaluate prefrontal cortex, primary visual cortex, and additional areas of hippocampus, in order to determine whether spine loss in schizoprhenia is localized or generalized.

描述：(申请人提供)在之前的一项研究中，我们发现了一个深刻的 左侧锥体神经元顶端树突上的棘突丢失 精神分裂症患者的下丘脑，受试者之间没有重叠 有精神分裂症和没有精神疾病的人。此外，还有 显著减少了这些细胞的顶端皮损，但 不是在它们的基底树状乔木中，也不是在金字塔的树状乔木中 邻近大脑皮层的神经元。自从完成这项研究以来，我们已经 改进了我们的快速高尔基体染色技术，因此现在可以应用 来自前抗精神病药物时代的组织，氯马林已经超过50年了 好几年了。此外，高尔基体神经元的数量现在已经足够了。 允许对神经元进行随机抽样以进行评估。其他人也有类似的发现 研究人员检查了大脑的其他区域，我们自己的数据显示 下丘脑MAP2异常，支持认知储备减弱 记录了认知和临床恶化的纵向过程， 所有人都支持将突触连接性降低作为基础的概念 精神分裂症。 我们现在建议使用改进的高尔基染色来研究5组20人 个人顺序：(1)评估我们以前的可复制 找到了。(2)确定档案中是否存在类似的异常 来自精神分裂症患者的大脑，这些患者在引入 抗精神病药物。有可能这些药物会导致脊椎的丧失， 他们会保护自己不受感染，或者他们两者都不会。(3)确定是否 类似的异常也出现在年轻精神分裂症患者的大脑中。 受试者，这将有助于确定脊柱的损失是否更多 很可能是精神分裂症的原因或结果，以及它是否是进行性的。(4) 评估前额叶皮质、初级视觉皮质和其他脑区 海马区，以确定精神分裂症患者的脊椎丢失是否 局部化的或泛化的。