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。虽然高尔基方法在精神分裂症的组织学上取得了一些最有说服力的发现，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。我们已经开发了一种新的高尔基-考克斯方法的改进，它产生了前所未有的可靠性，在70多个连续尸检病例的100多个连续块中进行了一致的染色。染色的神经元分布均匀，允许对神经元进行系统随机采样以进行分析。我们建议使用这种材料来研究年龄和性别匹配的20名精神分裂症患者和40名非精神疾病患者的树突分枝和脊柱密度，这些患者都是通过心理尸检进行临床评估的。我们将分析背侧(BA9)和腹侧(BA45)前额叶皮质以及海马结构(下丘、CA3、CA1和齿状回)的树突分枝和棘突密度。由于从块中切下的每一张切片都染色良好，我们建议与希望进行额外分析的其他实验室共享这些幻灯片。这项申请还包括继续我们在马其顿共和国正在进行的脑标本收集和心理尸检。这一收集为我们的高尔基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，无论是在我们的系里还是在其他机构。标本和数据保存在我们的科室，并经过严格的临床、神经病理学和毒理学审查。 公共卫生相关性： 精神分裂症是一种毁灭性的疾病，影响着1%的人口。精神分裂症背后的大脑结构异常知之甚少，但它们很可能涉及从神经元向外延伸的树突过程。我们已经开发了改进的程序，通过尸检在人脑组织中可视化这些过程，我们将使用这些方法来确定精神分裂症患者是否存在一致的大脑结构异常。

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.