NEUROPATHOLOGY

说明：这是第一次申请继续资助 神经病理学部分，旨在测试假设，一个特定的 GABA能系统的调节异常， 皮质锥体和非锥体神经元的多巴胺能神经支配。在 在过去的几年里，首席研究员已经聚集了相当多的人， 有证据支持GABA能系统被改变的假设， 精神分裂症此外，在过去的授予期间， 研究人员能够开发定位D1和D2受体技术， 测量谷氨酸神经元纤维直径，并表明GAD-IR终末 在精神分裂症患者的前扣带皮层发生了改变。校长 研究者还发现，TH-IR静脉曲张在 精神分裂症，并证明了两者之间的高度相关性 测量.这些都是新奇有趣的发现。 本计划项目申请的神经病理学部分旨在 继续贝尼斯博士正在进行的和高度重视的工作， 前额叶GABA和儿茶酚胺系统的神经化学解剖 死后大脑样本的扣带皮层这项工作将复制， 在某些领域，早期的大量工作，利用 免疫细胞化学和高分辨率受体放射自显影技术。一 这项计划工作中特别有希望的组成部分是不仅研究 精神分裂症患者前扣带回的神经化学解剖学研究 对照组，但包括双相情感障碍受试者组， 精神分裂症患者和双相患者的一级亲属，以及 一系列正常的，没有精神病的青少年这种方法应该 帮助解决（过去从本实验室记录的）变更是否 与遗传因素相关和/或与可能的异常 发展过程。

Description: This is the first submission for continued funding of the neuropathology section which aims to test the hypothesis that a specific dysregulation of the GABA-ergic system in tandem with alterations in dopaminergic innervation of cortical pyramidal and non-pyramidal neurons. In the past few years, the principal investigator has amassed a considerable body of evidence which supports the hypothesis that the GABAergic system is altered in schizophrenia. Additionally, over the past granting period the principal investigator was able to develop techniques to localize D1 and D2 receptors, measure glutamate neuron fiber diameters, and to suggest that GAD-IR terminals in the anterior cingulate cortex are altered in schizophrenia. The principal investigator has also found that TH-IR varicosities are similarly altered in schizophrenia and demonstrated a high degree of correlation between the two measurements. These are novel and interesting findings. The neuropathology section of this program project application is designed to continue Dr. Benes' ongoing and highly regarded work examining the neurochemical anatomy of the GABA and catecholamine systems in the anterior cingulate cortex of postmortem brain samples. This work would replicate, and in some areas extend, an extensive body of earlier work, utilizing immunocytochemical and high-resolution receptor autoradiography techniques. A particularly promising component of this planned work is to not only study the neurochemical anatomy of the anterior cingulate in schizophrenics and controls, but to include groups of subjects with bipolar disorder, first-degree relatives of both schizophrenics and bipolar patients, as well as a series of normal, non-psychiatrically ill teenagers. This approach should help to resolve if the changes (noted in the past from this laboratory) are associated with genetic factors and/or related to possible abnormal developmental processes.