HIPPOCAMPAL GENE EXPRESSION IN SCHIZOPHRENIA

描述（申请人摘要）：这是一个R21的请求， 针对RFA MH-00-002的“精神分裂症中的海马基因表达” 神经系统中的基因表达我们建议研究 正常人和精神分裂症患者海马区的基因 使用基因阵列技术和原位杂交的组合。这 研究项目被整合到我们正在进行的异常电路研究中， 精神分裂症患者的海马体具体来说，我们将测试假设 GABA能神经元的异常会导致 海马神经元亚群中的基因。我们将研究两组 精神分裂症患者，有（T+）和无（T-）治疗史的患者 在死亡前6个月内服用过精神抑制药物精神分裂症患者 正常对照组由相同数量的雄性和 女性主题 基因阵列技术将被用来筛选大量的候选基因 和EST。初步研究将进行对照与对照比较， 确定正常人群中基因表达的变异量。 此信息将用于确定差异 可以认为精神分裂症患者和对照之间的表达是显著的。 将在每组中合并几例受试者的脑组织样本， 在组间比较中实现更高的信噪比。基因 进一步研究的兴趣将被定义为具有a）显著的 在精神分裂症中的不同表达，B）中枢神经系统中的已知功能， 神经系统和精神分裂症的表达改变，和c）差异 在（T-）而不是（T+）精神分裂症组中表达。感兴趣的基因 然后将在完整的人脑组织中进行原位杂交研究， 确认精神分裂症的差异表达，并研究亚区域 和细胞定位。总的来说，这项研究中概述的基因图谱 该提案将是一个强有力的工具，以获得有关分子的信息， 精神分裂症患者海马体的异常述新基因阵列 技术将完全融入现有的研究计划， 海马功能障碍的分子、细胞和系统方面， 精神分裂症

DESCRIPTION (Applicant's abstract): This is a request for an R21 entitled "Hippocampal Gene Expression in Schizophrenia" in response to the RFA MH-00-002 "Gene Expression in the Nervous System". We propose to study the expression of genes in the hippocampus of normal subjects and patients with schizophrenia using a combination of gene array technology and in-situ hybridization. This research project is integrated into our ongoing study of abnormal circuitry in the hippocampus in schizophrenia. Specifically, we will test the hypothesis that an abnormality of GABAergic neurons will result in an abnormal expression of genes in subsets of hippocampal neurons. We will study two groups of schizophrenic patients, those with (T+) and without (T-) a history of treatment with neuroleptic drugs within 6 months prior to death. Both the schizophrenic and the normal control groups will be comprised of an equal number of male and female subjects. Gene array technology will be used to screen a large number of candidate genes and ESTs. Initial studies will make control vs. control comparisons to determine the amount of variation in gene expression in the normal population. This information will be used to determine the threshold at which differential expression between schizophrenics and controls can be considered significant. Brain tissue samples of several subjects will be pooled in each group to achieve a higher signal-to-noise ratio in the between-group comparisons. Genes of interest for further studies will be defined as having a) a markedly different expression in schizophrenia, b) a known function in the central nervous system and altered expression in schizophrenia, and c) differential expression in the (T-), but not (T+) schizophrenia groups. Genes of interest will then be studied with in situ hybridization in intact human brain tissue to confirm differential expression in schizophrenia and to study the subregional and cellular localization. Overall, gene profiling as outlined in this research proposal will be a powerful tool to gain information about molecular abnormalities in the hippocampus of schizophrenic subjects. The new gene array technology will be fully integrated into an existing research program to study the molecular, cellular, and systems aspects of hippocampal dysfunction in schizophrenia.