in vivo imaging of transplanted human induced-Pluripotent Stem Cell (iPSC) derived neurons to model neurological and psychiatric disorders

对移植的人类诱导多能干细胞 (iPSC) 衍生的神经元进行体内成像，以模拟神经和精神疾病

• 批准号: 9895863
• 负责人: Krishnan Padmanabhan
• 金额: $ 47.76万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895863
• 关键词: Action Potentials; Address; Affect; American; Anatomy; Animals; Antipsychotic Agents; Area; Attention; Autopsy; Brain; Calcium; Cell Differentiation process; Cell physiology; Cells; Code; Cognitive deficits; Complex; Computing Methodologies; Data; Delusions; Development; Disease; Disease Marker; Disease model; Early identification; Expressed Emotion; Fire - disasters; General Population; Goals; Hallucinations; Head; Health Care Costs; Homelessness; Human; Human Activities; Image; In Vitro; Individual; Label; Laser Scanning Microscopy; Life Expectancy; Memory; Mental disorders; Methods; Modeling; Monitor; Morphology; Mus; Neurites; Neurobiology; Neurological Models; Neurons; Pathology; Patients; Pattern; Physiological; Physiology; Pluripotent Stem Cells; Population; Process; Public Health; Research; Schizophrenia; Shapes; Structure; Substance abuse problem; Symptoms; Synapses; System; Technology; Testing; Time; Tissues; Transplantation; Validation; Work; area striata; awake; base; calcium indicator; gray matter; human disease; imaging modality; in vivo; in vivo calcium imaging; in vivo imaging; induced pluripotent stem cell; insight; nerve stem cell; nervous system disorder; neural circuit; neuropsychiatric disorder; novel; patient population; relating to nervous system; stem cells; suicidal risk; tool; two-photon

Project Summary 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 induced- Pluripotent Stem Cells (iPSCs) into an animal system and imaging the structure and function of these cells in vivo. In Aim 1, this project will develop the technologies needed to perform structural characteriation of human iPSC-derived neurons including developing methods to analyze neural circuit structure and anatomical dynamics. In Aim 2, this project will develop technologies needed to image the population calcium activity of human iPSC-derived neurons in vivo and develop new analysis methods for studying and characterizing this acitivity. In Aim 3, this project will apply these technologies to characterize the structure and spontaneous activity patterns of human iPSC-derived neurons in vivo. Taken together, this work will develop a powerful new platform for dissecting the structure and function of human neural circuits with the aims of understanding the neurobiological basis of schizophrenia.

项目总结