CYTOMETRIC AND IMMUNOCYTOCHEMICAL CORRELATES IN SCHIZOPHRENIC PREFRONTAL CORTEX

精神分裂症患者前额叶皮层的细胞计数和免疫细胞化学相关性

• 批准号: 6243064
• 负责人: CSABA LERANTH
• 金额: $ 28.51万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243064
• 关键词: Macaca mulatta; afferent nerve; antireceptor antibody; brain electrical activity; brain mapping; cellular pathology; disease /disorder model; dopamine receptor; electron microscopy; frontal lobe /cortex; histology; histopathology; human tissue; immunochemistry; immunocytochemistry; interneurons; neural degeneration; neurotransmitter receptor; schizophrenia; sensory cortex; synapses; visual cortex

The long range goal of this project is to anatomically dissect the intrinsic circuit organization of the prefrontal cortex at light and electron microscopic levels in normal humans, monkeys, and in selected instances, schizophrenic brains. Emphasis continues to be placed on the cytoarchitecture, local circuits, and monoaminergic innervation of associational and selected sensory cortical regions, with reference to findings obtained on schizophrenic brains in this and other laboratories. The project is subdivided along three lines of inquiry. 1) In ongoing investigations of neuropathological changes in schizophrenic cortex, we propose to add a new cohort of cases as well as expand cytometric investigation to include area 8, the human frontal eyefields, and area 45, Broca's area; we hope to confirm and extend evidence of increased cell density and decreased neuropil obtained in Brodmann's area 9 and 46, and determine whether cellular changes are specific to association areas and, within these areas, to specific neuronal populations; 2) Studies of intrinsic circuitry in human prefrontal cortex will address whether increased cell density in schizophrenics is due to loss or rearrangement of intracortical connections and/or atrophy of dendritic arborizations using fluorescent tracers, e.g., diI, and Golgi impregnations, respectively. Inputs to identified inhibitory interneurons will also be examined in rhesus monkeys and human cortex in immunocytochemical analyses at the light and electron microscopic level; 3) We will proceed with the ultrastructural characterization of the synaptic architecture of chemically defined afferents on identified cortical targets, guided by the hypothesis that norepinephrine, serotonin, and acetylcholine each have preferential patterns of termination within the cortical mantle just as we demonstrated for the dopaminergic innervation. Double labeling immunocytochemical paradigms will also be used to reveal anatomical substrates of the interaction among these systems in the prefrontal cortex of rhesus monkeys, and ultimately in the human brain. The availability of neurotransmitter - and receptor-specific antibodies and mRNA probes which recognize receptor-synthesizing neurons, some of which are being developed in Project III of this proposed Center, will allow us to gain a comprehensive view of pre-and postsynaptic elements of specific neurotransmitter systems and thereby to gain a more explicit understanding of their psychoactive efforts.

该项目的长期目标是从解剖学角度剖析 前额皮质在光照和光照条件下的内在电路组织 正常人、猴子和选定的人体内的电子显微镜水平 例如，精神分裂症的大脑。 重点仍然放在 细胞结构、局部回路和单胺能神经支配 关联和选定的感觉皮层区域，参考 在该实验室和其他实验室中对精神分裂症患者的大脑获得的研究结果。 该项目按照三个调查方向细分。 1) 正在进行中 通过研究精神分裂症皮质的神经病理学变化，我们 建议添加新的病例组并扩大细胞计数 调查范围包括区域 8、人类额叶视野和区域 45、布罗卡区；我们希望确认并扩展增加的证据 Brodmann 区 9 和 46 中获得的细胞密度和神经纤维减少， 并确定细胞变化是否特定于关联区域 并且，在这些区域内，针对特定的神经元群体； 2）研究 人类前额叶皮层的内在电路将解决是否 精神分裂症患者的细胞密度增加是由于丢失或重排造成的 皮质内连接和/或树突状树枝萎缩 使用荧光示踪剂，例如 diI 和高尔基浸渍， 分别。 已识别的抑制性中间神经元的输入也将是 在恒河猴和人类皮质中进行免疫细胞化学检查 在光学和电子显微镜水平上进行分析； 3）我们将继续 具有突触结构的超微结构特征 化学定义的传入已识别的皮质目标，引导 假设去甲肾上腺素、血清素和乙酰胆碱各自 在皮质地幔内有优先的终止模式 正如我们所演示的多巴胺能神经支配。 双标签 免疫细胞化学范例也将用于揭示解剖学 前额叶这些系统之间相互作用的基础 恒河猴的皮质，最终进入人脑。 这 神经递质和受体特异性抗体的可用性以及 识别受体合成神经元的 mRNA 探针，其中一些 正在该拟议中心的项目 III 中开发，将允许 我们获得突触前和突触后元素的全面了解 特定的神经递质系统，从而获得更明确的 了解他们的心理活动。