ENGRAFTING HUMAN NEURONS INTO ANIMAL MODELS TO STUDY SCHIZOPHRENIA

精神分裂症影响着世界上超过1%的人口，其中包括300万美国人，精神分裂症是一种令人衰弱的疾病 精神障碍以一系列症状为特征，包括幻觉、妄想、困难 表达情绪，以及注意力和记忆力的缺陷。尽管目前有抗精神病药物， 精神分裂症患者的预期寿命比普通人群低10年， 容易滥用药物，无家可归，并有自杀的危险。因此，对这两个国家征收的通行费 患有这种疾病的个人的生命和公共卫生成本是巨大的。目前没有 治疗精神分裂症，并研究疾病的原因，包括解剖学和生理学 大脑的破坏，一直是困难的，因为对细胞的潜在病理知之甚少。 病人。 为了阐明在精神分裂症患者中发现的解剖和生理缺陷，这 一项提案将通过移植重新编程的人类诱导物来开发一种新的疾病模型 将多能干细胞(IPSCs)植入动物系统。在这笔赠款的指导部分，解剖学 (目标1)和(目标2)发生在精神分裂症患者神经元中的生理缺陷将是 特色化的。这两个目标都在进行中，精神分裂症干细胞已经成功植入 老鼠。此外，研究人体解剖和生理复杂性的新的计算方法 这些细胞已经发育出来了。基于前两个目标的发现，独立的 本提案的一部分(目标3)将涉及在个体中发现的解剖和生理紊乱 细胞对患者被破坏的神经元活动的整体模式的影响。 拟议中的研究有可能为了解糖尿病的生物学基础提供基本的见解。 精神分裂症。在这个项目中开发的结果和工具将促进对 神经功能，并可能为筛选新药疗法的高通量分析铺平道路 用来治疗这种疾病。

Affecting over 1% of the world’s population, including 3 million Americans, schizophrenia is a debilitating psychiatric disorder characterized by an array of symptoms including hallucinations, delusions, difficulty expressing emotions, and deficits in attention and memory. Despite the currently available antipsychotics, patients suffering schizophrenia have a life expectancy 10 years lower than that of the general population, are prone to substance abuse, homelessness, and are at risk of suicide. As a result, both the toll exacted on the lives of individuals suffering from the disorder and the public health costs are substantial. There is currently no cure for schizophrenia, and research into the causes of the disease, including the anatomical and physiological disruptions in the brain, has been difficult because little is known about the underlying pathology of cells in patients. To elucidate the anatomical and physiological deficits found in the patients with schizophrenia, this proposal will develop a novel model for the disorder by transplanting reprogrammed human inducible pluripotent stem cells (iPSCs) into an animal system. During the mentored portion of this grant, the anatomical (Aim 1) and physiological deficits (Aim 2) that occur in neurons derived from patients with schizophrenia will be characterized. Both aims are underway, and schizophrenia stem cells have been successfully engrafted into mice. Additionally, novel computational methods for studying the anatomical and physiological complexity of these cells have been developed. Based on the discoveries made in the first two aims, the independent portion of this proposal (Aim 3) will relate the anatomical and physiological disruptions identified in individual cells to the global patterns of neuronal activity that are disrupted in patients. The proposed studies have the potential to provide fundamental insights into the biological basis of schizophrenia. The results and tools developed in this project will advance the basic understanding of neuronal function, and could pave the way for high-throughput assays with which to screen new drug therapies for the treatment of the disorder.