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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Kovoor 博士目前是罗德岛大学的助理教授。 抗精神病药物彻底改变了精神分裂症和其他相关精神疾病的治疗。 然而，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的、使人衰弱的运动障碍（Rascol 和 Fabre，2001；Llorca 等，2002；Casey，2004；Margolese 等，2005）。 L-DOPA 引起的运动障碍 (LID) 是帕金森病药物治疗的一种类似的无法解释的、使人衰弱的毒性（Brotchie 等，2005）。 这项资助的试点拨款提案旨在测试这样的假设：经过基因改造以表达 RGS9-2 并植入纹状体的小鼠胚胎干细胞可以治疗 TD 和 LID。 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 RGS9 2，并且该表达在 ES 细胞的神经元分化时不会沉默。 具体目标 2：我们将用来自具体目标 1 的 RGS9 2 构建体稳定转染的 ES 细胞系植入运动障碍 RGS9 敲除小鼠中，并量化植入前后异常不自主运动的水平。