THE MEDIODORSAL THALAMIC NUCLEUS IN SCHIZOPHRENIA

精神分裂症的丘脑内侧核

• 批准号: 6528130
• 负责人: JOSEPH N PIERRI
• 金额: $ 14.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6528130
• 关键词: Macaca fascicularis; cellular pathology; clinical research; gene expression; human subject; immunocytochemistry; in situ hybridization; microarray technology; molecular pathology; neuroanatomy; neurons; schizophrenia; thalamus

DESCRIPTION: (Adapted from applicant's abstract) Schizophrenia is a common, devastating illness, which most often leads to life long disability. Despite recent advances, the cellular and molecular pathophysiology of this illness remains unknown. In this mentored career development award, the candidate will test the general hypothesis that projection neurons in the mediodorsal thalamic nucleus (MDTN) are abnormal in schizophrenia, and that this abnormality is associated with alterations in the pattern of gene expression in the MDTN. Recent postmortem studies have reported that the MDTN is smaller in size and has fewer neurons and glial cells in subjects with schizophrenia compared to normal subjects. The results of these studies have raised the following questions that will be addressed in the proposed studies: 1) Is a decrease in neuronal number and volume of the MDTN common in schizophrenia, and is it diagnostically specific to the illness? 2) Which neuronal subpopulations are affected- local circuit neurons or neurons that project to the prefrontal cortex? 3) What alterations in MDTN gene expression are associated with, and potentially causal to these abnormalities? 4) Are these findings part of the pathophysiology of the illness or are they the result of chronic treatment with antipsychotic medications? While investigating these questions, the candidate, a child psychiatrist, will under take a program of study to develop skills in 1) the conduct of rigorous human postmortem studies, 2) the techniques of stereology, immunohistochemistry, and in situ hybridization, and 3) the analysis of patterns of tissue specific gene expression in psychiatric disease. Finally, he will learn how to use a nonhuman primate model of clinical phenomena to understand human disease and treatment. Acquiring these skills at the University of Pittsburgh, under the mentorship of Professors David A. Lewis and Pat R. Levitt, will enable the candidate to launch a career investigating the developmental pathophysiology of psychiatric disorders which have their onset in childhood and adolescence.

描述：（改编自申请人的摘要）精神分裂症是一种常见的， 毁灭性的疾病，通常会导致终身残疾。尽管 最近的进展，这种疾病的细胞和分子病理生理学 仍然未知。在这个指导职业发展奖，候选人将 检验一般假设，即丘脑背内侧核的投射神经元 核（MDTN）在精神分裂症中异常，这种异常是 与MDTN中基因表达模式的改变相关。 最近的尸检研究报告说，MDTN的大小较小， 精神分裂症患者的神经元和神经胶质细胞比 名正常人这些研究的结果提出了以下几点 在拟议的研究中将解决的问题：1）是减少 神经元数量和体积的MDTN常见于精神分裂症，它是 具体到疾病的诊断？2)哪些神经元亚群 受影响的-局部回路神经元或投射到前额叶的神经元 皮质？3)MDTN基因表达的改变与 可能与这些异常有关吗4)这些发现是 疾病的病理生理学或它们是长期治疗的结果， 抗精神病药物 在调查这些问题时，候选人，儿童精神病学家，将 在采取一项研究计划，以发展技能1）进行严格的 人体死后研究，2）体视学技术， 免疫组化和原位杂交，以及3）分析 精神疾病中组织特异性基因表达的模式他总算 将学习如何使用临床现象的非人类灵长类动物模型， 了解人类疾病和治疗。获得这些技能， 匹兹堡大学，在教授大卫A。刘易斯和 帕特河莱维特，将使候选人启动职业生涯调查 精神障碍的发展病理生理学， 在童年和青春期。