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

基本信息

批准号：
8402635
负责人：
Karin Borgmann-Winter
金额：
$ 16.34万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
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/8402635
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

项目摘要

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）：该提案寻求一段时间的监督科学培训，以使医学博士 Karin Borgmann-Winter 发展成为一名独立的医师科学家。背景：早期干预对于精神分裂症高危年轻人至关重要；然而，抗精神病药物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，不同的抗精神病药物可能会影响大脑的神经营养或神经发育作用。然而，这些研究是在动物大脑或体外细胞系中进行的，但从未在源自患者的神经细胞中进行。研究项目：本研究将探讨抗精神病药物对患有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，检查神经元发育的分子和细胞生物学过程与临床嗅觉测量和症状进展的相关性。我们将在抗精神病药物治疗前后检查精神病个体嗅觉活检组织神经元中的这些因素。我们将开发来自年轻精神病患者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物之间的关系、它们的神经递质结合谱和 BDNF-TrkB 信号传导，作为抗精神病药物影响神经发育的可能机制。环境：主要培训地点是细胞和分子神经病理学项目、神经生物学和行为中心哈恩实验室以及宾夕法尼亚大学精神分裂症研究中心。由医学博士 Raquel E. Gur、医学博士 Steven Arnold 和医学博士 Chang-Gyu Hahn 领导的多学科指导将促进基础科学方法论和青年精神病患者临床观察的双向转化。研究职业发展：指导和正式课程将满足候选人的职业发展需求：1) 获得设计和实施更复杂的细胞和分子生物学实验室方法所需的额外技能。 2) 接受心理物理嗅觉测试管理和嗅觉数据解释方面的培训。 3) 培养评估和招募精神分裂症高危青少年和精神病早期阶段青少年的额外技能。 4) 发表研究成果并提交RO1。相关性：该提案将研究抗精神病药物对发育中的神经组织的潜在神经毒性或神经发育影响。这些信息对于确定早期干预对年轻人大脑发育的影响至关重要。