Transcriptional Regulation of Metabolism in Schizophrenia

精神分裂症代谢的转录调控

基本信息

批准号：
7793386
负责人：
Rita Marie Cowell
金额：
$ 13.44万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7793386
关键词：
Abbreviations Accounting Acetylation Address Adult Affect Autopsy Brain CREB1 gene Cell Culture Techniques Chromatin DNA Methyltransferase DNA Modification Methylases Data Deoxycytidine Development Development Plans Educational workshop Epigenetic Process Ethics Event Exposure to Functional disorder Funding GABA transporter GLUT4 gene Gene Expression General Population Genes Goals Health Histone Acetylation Histone Deacetylase Homelessness Homeostasis Human Hypoxia In Vitro Injury Interneurons Knowledge Life Long-Term Effects Medical Mental Health Metabolic Metabolism Methylation Neurons Pathogenesis Pathway interactions Patients Perinatal Perinatal Hypoxia Peroxisome Proliferator-Activated Receptors Population Predisposition Process Production Research Research Personnel Rodent Model Role Schizophrenia Signal Transduction Synapses Synaptic plasticity Synaptophysin Technical Expertise Testing Training Transcriptional Regulation Trichostatin A Valproate Sodium Valproic Acid base brain tissue career career development cost cytochrome c oxidase design experience fatty acid metabolism glucose transport glutathione peroxidase high risk improved in vivo inhibitory neuron interest laser capture microdissection myocyte-specific enhancer-binding factor 2 neuron loss postnatal prevent programs research study success symposium transcription factor

项目摘要

DESCRIPTION (provided by applicant): For much of her scientific research career, Dr. Cowell has studied the cellular mechanisms underlying neuronal cell death and injury. However, she has recently made a significant change in long-term research interests and is in the process of entering the field of mental health research. This proposal outlines a strategy for didactic and technical training and exposure to emerging concepts in translational schizophrenia research, with the goal of promoting Dr. Cowell's success as an independent, extramurally funded, academic investigator in mental health. Dr. Cowell's development plan involves the completion of coursework and attendance at research conferences, workshops in career development and ethical conduct in research, and a program of research that will contribute technically and intellectually to her progress towards independence. Based on preliminary data suggesting that peroxisome proliferator activated receptor g (PPARg) coactivator 1a (PGC-1a) is involved in metabolic homeostasis in inhibitory neurons, experiments are designed to test the hypotheses that 1) PGC-1a regulates metabolism and synaptic plasticity in GABAergic neurons in vitro and in vivo, 2) adverse perinatal events (hypoxia) have a long-term effect on the maturation of GABAergic circuits by disrupting normal PGC-1a expression and histone acetylation in development, and 3) the expression levels of PGC-1a and related metabolic genes are altered in inhibitory interneurons in the cortex of schizophrenic patients. To test these hypotheses, Dr. Cowell has chosen a panel of consultants with extensive experience in cell culture, rodent models of perinatal hypoxia, assessment of chromatin acetylation/methylation status, and laser capture microdissection from human postmortem brain tissue. This plan will equip the applicant with the knowledge and technical expertise to address key issues in mental health research, while elucidating the mechanisms by which disturbances in brain development contribute to the pathogenesis of schizophrenia. Schizophrenia is a significant health concern; it has been estimated that 1% of the general population and 14% of the homeless population has schizophrenia. In 1990 alone, schizophrenia accounted for $32.5 billion in medical costs. New treatments are needed to improve the lives of those with schizophrenia and to prevent the emergence of schizophrenia in high-risk populations.

描述（由申请人提供）：在她的大部分科学研究生涯中，Cowell博士都研究了神经元细胞死亡和损伤的细胞机制。但是，她最近在长期研究兴趣上做出了重大变化，并且正在进入心理健康研究领域。该提案概述了教学和技术培训的策略，并在转化精神分裂症研究中介绍了新兴概念，目的是促进Cowell博士作为一名独立，外部资助的，精神健康的学术研究者的成功。 Cowell博士的发展计划涉及完成研究会议的课程和出席，研究会议，职业发展和研究中的道德行为以及一项研究计划，该计划将在技术上和智力上为她在独立方面的进步做出贡献。 Based on preliminary data suggesting that peroxisome proliferator activated receptor g (PPARg) coactivator 1a (PGC-1a) is involved in metabolic homeostasis in inhibitory neurons, experiments are designed to test the hypotheses that 1) PGC-1a regulates metabolism and synaptic plasticity in GABAergic neurons in vitro and in vivo, 2) adverse perinatal事件（缺氧）通过破坏正常的PGC-1A表达和发育中的组蛋白乙酰化对GABA能回路的成熟具有长期影响，而3）PGC-1A和相关代谢基因的表达水平在精神分裂症患者的皮质中的抑制性膜中改变。为了检验这些假设，Cowell博士选择了一组具有丰富经验在细胞培养的顾问，围产期缺氧的啮齿动物模型，评估乙酰化乙酰化/甲基化状态以及激光从人类后体脑脑组织中捕获显微解剖。该计划将使申请人获得知识和技术专长，以解决心理健康研究中的关键问题，同时阐明了大脑发育中障碍有助于精神分裂症的发病机理的机制。精神分裂症是一个重大的健康问题。据估计，1％的普通人群和14％的无家可归人群患有精神分裂症。仅在1990年，精神分裂症就占医疗费用的325亿美元。需要新的治疗方法来改善精神分裂症患者的生活，并防止高危人群中精神分裂症的出现。