A Macedonian Center for Ultrastructural Studies in Schizophrenia

描述（由申请人提供）：精神分裂症的神经病理学特征仍然难以捉摸。高尔基体研究揭示了较低的密度树突棘，与非精神病患者相比，在额叶皮层和下托。然而，它们不能提供足够的分辨率来确定棘是否真的丢失或异常小，以及可见的棘结构是否正常。在体内成像研究，遗传协会，和生化研究表明，髓鞘在白色物质可能是异常薄或可能包含病灶的破坏;光学显微镜研究白色物质迄今为止揭示很少，最多只能显示间接证据，这种异常。精神分裂症形态学中的这些重要问题可以通过超微结构研究得到最好的解决。我们建议在马其顿建立一个电子显微镜（EM）设施，培训人们进行和解释电子显微镜（特别是大脑），并让他们开始研究精神分裂症的这些问题。特别是，我们提出了定量措施的脊柱体积和相对频率的形态类型的脊柱在额叶皮层和下托，视神经，胼胝体和扣带束的轴突和髓鞘直径的措施。大学医学院之间的长期合作。马其顿共和国斯科普里的西里尔和美多迪乌斯}、纽约州立精神病研究所和哥伦比亚大学已经从患有和不患有精神疾病的受试者中收集了正在进行的尸检大脑。该收集用于美国和加拿大的许多资助研究，将构成马其顿拟议研究的基础，从临床、神经病理学和毒理学特征良好的病例中提供适当材料。一台功能齐全的JEOL 100x12电子显微镜和所有必要的辅助设备已运往马其顿，等待安装。一位有经验的电子显微镜学家将管理EM实验室，并培训人们使用它。其中一名受训人员将前往美国接受神经系统EM专家的进一步培训，然后返回马其顿，在监督下完成研究。公共卫生相关性：精神分裂症是一种导致终身残疾的常见疾病。与许多其他脑部疾病相比，大脑中的关键结构变化尚未被明确确定。间接证据表明，结构变化很可能局限于树突棘和髓鞘，大脑结构的细节只能通过电子显微镜观察。我们建议在马其顿建立一个电子显微镜设施，在那里我们将收集尸体解剖的大脑，并检查它们，看看这些异常是否存在。对大脑结构异常的结论性和详细的了解对于了解疾病的原因和找到有效的治疗或治愈方法至关重要。

DESCRIPTION (provided by applicant): The neuropathological features of schizophrenia remain elusive. Golgi studies reveal a lower density of dendritic spines, compared with nonpsychiatric subjects, in frontal cortex and subiculum. However, they do not afford sufficient resolution to ascertain whether spines are truly lost or rather abnormally small, and whether the visible spines are structurally normal. In vivo imaging studies, genetic associations, and biochemical studies suggest that myelin sheaths in the white matter might be abnormally thin or might contain foci of disruption; light microscopic studies of white matter have so far revealed little, and at best could show only indirect evidence of such abnormalities. These important issues in the morphology of schizophrenia can be best resolved by ultrastructural studies. We propose to establish an electron microscope (EM) facility in Macedonia, to train people to perform and interpret electron microscopy (particularly of the brain), and to have them start to work on these problems in schizophrenia. In particular, we propose quantitative measures of spine volumes and relative frequencies of morphological types of spines in frontal cortex and subiculum, and measures of axonal and myelin sheath diameters in optic nerve, corpus callosum, and cingulum bundle. A longstanding collaboration between the School of Medicine of the University }Ss. Cyril & Methodius} in Skopje, Republic of Macedonia, and the New York State Psychiatric Institute and Columbia University has produced an ongoing collection of autopsy brains from subjects with and without psychiatric illnesses. This collection, used for numerous funded studies in the US and Canada, will form the basis for the proposed study in Macedonia, supplying appropriate material from cases that are well- characterized clinically, neuropathologically, and toxicologically. A fully functional JEOL 100x12 electron microscope and all needed ancillary equipment have been shipped to Macedonia and await installation. An experienced electron microscopist will run the EM laboratory and will train people in its use. One such trainee will come to the United States for further training by experts in EM of the nervous system, and will then return to Macedonia for supervised completion of the studies. PUBLIC HEALTH RELEVANCE: Schizophrenia is a common disease that produces lifelong disability. In contrast to many other brain diseases, the critical structural changes in the brain have not been definitively identified. Indirect evidence suggests that structural changes are likely to be localized in dendritic spines and myelin sheaths, brain structures whose details can be visualized only by electron microscopy. We propose to establish an electron microscope facility in Macedonia, where we will collect autopsy brains and examine them to see if these abnormalities are present. Conclusive and detailed knowledge of the structural abnormalities of the brain are crucial too understanding the cause of the illness and to finding effective treatments or cures.