Golgi Studies of Schizophrenia

描述（申请人提供）：高尔基染色显示树突的解剖结构。虽然高尔基方法已经在精神分裂症中产生了一些最有力的组织学发现，但使用这些技术的研究并不常见，可能是因为这些技术很难应用，而且出了名的反复无常。我们开发了一种新的修改的高尔基-考克斯方法，产生了前所未有的可靠性，在70多个连续尸检病例的100多个连续块中保持一致的染色。有一个均匀分布的染色神经元，允许系统的随机抽样神经元进行分析。我们建议使用这些材料来研究20名按年龄和性别匹配的精神分裂症患者和40名无精神疾病的患者的树突树突和脊柱密度，所有这些患者都通过心理尸检进行临床评估。我们将分析背侧（BA9）和腹侧（BA45）前额皮质以及海马区（耻骨下、CA3、CA1和齿状回）的树突树突和脊柱密度。由于每块切片都染色良好，我们建议与其他希望进行额外分析的实验室共享载玻片。这项申请还包括继续我们正在马其顿共和国进行的脑标本收集和心理解剖。这个集合为我们的高尔基体研究和许多其他精神疾病的神经生物学研究提供了新鲜的组织，无论是在我们系还是在其他机构。标本和数据保存在我科，并经过严格的临床、神经病理和毒理学审查。

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.