Neuroprotective/Neurodevelopmental Effects-Antipsychotics in Adolescent Psychoses

神经保护/神经发育作用——青少年精神病中的抗精神病药物

• 批准号: 8598934
• 负责人: Karin Borgmann-Winter
• 金额: $ 16.33万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-20 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8598934
• 关键词: Address; Adolescent; Adverse effects; Affect; Affinity; Aftercare; Animals; Antipsychotic Agents; Apoptotic; Basic Science; Behavior; Binding; Biological; Biological Assay; Biological Process; Biopsy; Brain; Brain-Derived Neurotrophic Factor; Cell Line; Cells; Clinical; Clozapine; Complex; Cultured Cells; Cyclic AMP-Responsive DNA-Binding Protein; Data; Detection; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Early Intervention; Effectiveness of Interventions; Environment; Event; Exhibits; G-Protein-Coupled Receptors; GTP-Binding Proteins; Gur; Haloperidol; Human; In Vitro; Individual; Intervention Trial; Laboratories; Link; Measures; Mediating; Mentors; Mentorship; Methods; Molecular; Neurobiology; Neurons; Neurotransmitter Receptor; Neurotransmitters; Odors; Olfactory Epithelium; Olfactory Receptor Neurons; Patients; Pennsylvania; Physicians; Procedures; Process; Proto-Oncogene Proteins c-akt; Psychophysics; Psychotic Disorders; Publishing; Receptor Activation; Research; Research Project Grants; Risk; Risperidone; Schizophrenia; Scientist; Serotonin; Signal Transduction; Site; Smell Perception; Staging; Symptoms; System; Testing; Therapeutic Effect; Tissues; Training; Translations; Universities; career development; comparative; cytotoxicity; design; high risk; molecular array; nerve stem cell; neurodevelopment; neuroepithelium; neuron apoptosis; neuron development; neuropathology; neurotoxic; preclinical study; programs; protective effect; protein activation; public health relevance; receptor; receptor binding; relating to nervous system; skills; young adult

DESCRIPTION (provided by applicant): This proposal seeks a period of supervised scientific training to enable Karin Borgmann-Winter, M.D. to develop into an independent physician-scientist. Background: Early intervention is critically important for young individuals at high risk for the development of schizophrenia; yet the effects of antipsychotics on the developing brain are largely unknown. Pre-clinical studies suggested that different antipsychotics may impact on neurotrophic or neurodevelopmental effects in the brain. These studies, however, were conducted in animal brains or in vitro cell lines, but never in neural cells derived from patients. Research Project: This study will examine the potential neurodevelopmental/neurotrophic effects of antipsychotics in young subjects with psychoses. We will employ the olfactory system as a window in which to examine the molecular and cell biological processes of neuronal development in correlation with clinical olfactory measures and symptom progression. We will examine these factors in neurons from the olfactory biopsy tissues of psychotic individuals before and after antipsychotic treatment. We will develop in vitro cultures of olfactory receptor neurons derived from biopsy tissues from young individuals with psychoses and examine the relationships between different antipsychotics, their neurotransmitter binding profiles and BDNF- TrkB signaling as a possible mechanism for the effects of antipsychotics on neurodevelopment. Environment: The primary training sites are the Cellular and Molecular Neuropathology Program, the Hahn Laboratory of the Center for Neurobiology and Behavior and the Schizophrenia Research Center at the University of Pennsylvania. Multi-disciplinary mentoring led by and Raquel E. Gur, M.D., PhD, Steven Arnold, M.D. and Chang-Gyu Hahn, M.D. Ph.D. will facilitate bi-directional translation of methodological approaches in basic science and clinical observations in young individuals with psychoses. Research Career Development: Mentorship and formal coursework will address the candidate's career development needs to: 1) Acquire additional skills needed for the design and implementation of more complex cellular and molecular biological laboratory methods. 2) Obtain training in the administration of psychophysical olfactory tests and the interpretation of olfactory data. 3) Develop additional skills in the assessment and recruitment of adolescents at high risk for schizophrenia and in early stages of psychosis. 4) Publish research findings and submit an RO1. Relevance: This proposal will examine the potential neurotoxic or neurodevelopmental effects of antipsychotics on the developing neural tissues. Such information will be crucial for determining the effects of early intervention on the developing brains of young individuals.

描述（由申请人提供）：该提案寻求一段监督的科学培训，以使Karin Borgmann-Winter，M.D。能够发展成为独立的医师科学家。 背景：早期干预对于患有精神分裂症的高风险的年轻人至关重要；然而，抗精神病药对发育中的大脑的影响在很大程度上尚不清楚。临床前研究表明，不同的抗精神病药可能会影响大脑中神经营养或神经发育作用。但是，这些研究是在动物大脑或体外细胞系中进行的，但从未在患者中得出的神经细胞中进行。 研究项目：本研究将检查抗精神病药对精神病的年轻受试者的潜在神经发育/神经营养作用。我们将利用嗅觉系统作为一个窗口，在其中检查与临床嗅觉测量和症状进展相关的神经元发育的分子和细胞生物学过程。我们将在抗精神病药物治疗前后检查来自精神病患者嗅觉活检组织的神经元中的这些因素。我们将开发来自患有精神病的年轻人的活检组织的嗅觉受体神经元的体外培养物，并检查不同抗精神病药，其神经递质的结合谱和BDNF-TRKB信号传导之间的关系，作为抗神经神经传播作用的可能机制。 环境：主要训练地点是细胞和分子神经病理学计划，神经生物学与行为中心的Hahn实验室以及宾夕法尼亚大学的精神分裂症研究中心。由M.D. Raquel E. Gur和M.D.史蒂文·阿诺德（Steven Arnold，M.D。将促进基础科学方法中方法学方法的双向翻译和精神病年轻人的临床观察结果。 研究职业发展：指导和正式课程将解决候选人的职业发展所需的需求：1）获得设计和实施更复杂的细胞和分子生物实验室方法所需的其他技能。 2）获得心理物理嗅觉测试和嗅觉数据的解释的培训。 3）在评估和招募精神分裂症和精神病早期的高风险的青少年评估和招募方面发展额外的技能。 4）发布研究结果并提交RO1。 相关性：该建议将检查抗精神病药对发育中神经组织的潜在神经毒性或神经发育作用。此类信息对于确定早期干预对年轻人发展的大脑的影响至关重要。