EMBRYONIC MOUSE STEM CELLS REPAIR BRAIN TOXICITY CAUSED BY ANTIPSYCHOTIC DRUGS

小鼠胚胎干细胞修复抗精神病药物引起的脑毒性

• 批准号: 7725258
• 负责人: Abraham Kovoor
• 金额: $ 1.51万
• 依托单位: ROGER WILLIAMS HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725258
• 关键词: Antipsychotic Agents; Applications Grants; Brain; Chronic; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Development; Dyskinetic syndrome; ES Cell Line; Embryo; Functional disorder; Funding; Grant; Implant; Institution; Knockout Mice; Mental disorders; Movement Disorders; Mus; Neuronal Differentiation; Parkinson Disease; Pharmacotherapy; Research; Research Personnel; Resources; Rhode Island; Schizophrenia; Source; Stem cells; Tardive Dyskinesia; Testing; Toxic effect; United States National Institutes of Health; Universities; abnormal involuntary movement; design; embryonic stem cell; implantation; professor; repaired

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Kovoor is presently an assistant professor at the University of Rhode Island. Antipsychotic drugs have revolutionized the treatment of schizophrenia and other related mental disorders. However, a serious toxicity of chronic treatment with many antipsychotic drugs is the development of tardive dyskinesia (TD), an irreversible and debilitating movement disorder of unknown pathophysiology (Rascol and Fabre, 2001; Llorca et al., 2002; Casey, 2004; Margolese et al., 2005). L-DOPA-induced dyskinesia (LID) is a similar unexplained and debilitating toxicity of the pharmacotherapy of Parkinson's disease (Brotchie et al., 2005). The funded pilot grant proposal was designed to test the hypothesis that embryonic mouse stem cells genetically modified to express RGS9-2 and implanted into the striatum can treat TD and LID. The following two specific aims were proposed SPECIFIC AIM 1: We will test if mouse embryonic stem (ES) cells can stably express RGS9 2 and that expression is not silenced upon neuronal differentiation of the ES cells. SPECIFIC AIM 2: We will implant ES cell lines stably transfected with the RGS9 2 construct from Specific Aim 1 into dyskinetic RGS9 knockout mice and quantify the level of abnormal involuntary movements pre and post-implantation.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 博士科沃尔目前是罗得岛大学的助理教授。 抗精神病药物已经彻底改变了精神分裂症和其他相关精神障碍的治疗。 然而，用许多抗精神病药物长期治疗的严重毒性是迟发性运动障碍（TD）的发展，这是一种病理生理学未知的不可逆和使人衰弱的运动障碍（Rascol和法布尔，2001; Llorca等人，2002年;凯西，2004年; Margaret等人，2005年）。 L-DOPA诱导的运动障碍（LID）是帕金森病的药物治疗的类似的无法解释的和使人衰弱的毒性（Brotchie等人，2005年）。 资助的试点赠款提案旨在测试胚胎小鼠干细胞经遗传修饰以表达RGS 9 -2并植入纹状体可以治疗TD和LID的假设。 提出了以下两个具体目标 具体目标1：我们将测试小鼠胚胎干（ES）细胞是否可以稳定表达RGS 9 - 2，并且该表达在ES细胞的神经元分化后不沉默。 具体目标2：我们将植入ES细胞系稳定转染的RGS 9 - 2结构从特定的目标1到运动障碍RGS 9基因敲除小鼠和定量的水平异常不自主运动植入前和植入后。