Engrafting human neurons into animal models to study schizophrenia

描述（由申请人提供）：精神分裂症影响超过1%的世界人口，包括300万美国人，是一种使人衰弱的精神疾病，其特征是一系列症状，包括幻觉、妄想、情绪表达困难、注意力和记忆力缺陷。尽管目前有抗精神病药物可用，但精神分裂症患者的预期寿命比一般人群低10年，容易滥用药物，无家可归，并有自杀风险。结果，对患有这种疾病的人的生命和公共卫生造成了严重影响

DESCRIPTION (provided by applicant): 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 elucidat 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.