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Golgi Studies of Schizophrenia

Golgi Studies of Schizophrenia
精神分裂症的高尔基体研究
批准号:
6657999
负责人:
ANDREW J DWORK
金额:
$38.92万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-08-01 至 2006-07-31

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中文摘要
翻译
描述:(由申请人提供)在以前的研究中,我们发现了一个深刻的 左侧锥体神经元顶端树突棘缺失 精神分裂症个体的下托,受试者之间没有重叠 精神分裂症患者和非精神疾病患者。此外还有 是一个显着减少,在顶端的树突状乔木这些细胞,但 不是在它们的基底树突乔木,也不是在锥体的树突乔木, 邻近新皮层的神经元自从完成这项研究以来,我们 改进了我们的快速高尔基体染色技术,使其现在适用于 与神经抑制剂出现之前的组织相比较,这些组织已经在洛玛琳中存在了50多年 年此外,高尔基体浸渍的神经元的数量现在已经足够 以允许对神经元进行随机采样以进行评估。其他人的类似调查结果 研究人员检查了大脑的其他区域,我们自己的数据显示 海马下托MAP 2异常,支持认知储备减少,和 记录认知和临床恶化的纵向过程, 所有这些都支持突触连接性降低的概念, 精神分裂症 我们现在建议采用改良的高尔基体染色法来研究5组20个 (1)评估我们以前的可复制性 发现(2)为了确定存档中是否存在类似的异常, 精神分裂症患者的大脑, 神经抑制药这些药物可能会导致脊椎的丧失, 或者他们什么都不做(3)以确定是否 在幼年黑猩猩的大脑中也存在类似的异常 主题,这将有助于确定脊椎的损失是否更多 可能是精神分裂症的原因或结果,以及是否进行性。(四) 为了评估前额叶皮层、初级视觉皮层和其他区域, 海马体,以确定是否脊柱丢失在海马体, 局限性或普遍性。
英文摘要
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.
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