Prenatal stress and the development of inhibitory neurons in the forebrain

产前应激和前脑抑制性神经元的发育

• 批准号: 8103295
• 负责人: HANNA E STEVENS
• 金额: $ 17.14万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8103295
• 关键词: Acute; Address; Adolescent; Adult; Affect; Amygdaloid structure; Animal Model; Animals; Anxiety; Apoptotic; Area; Award; Behavior; Behavior Disorders; Behavioral; Brain; Brain-Derived Neurotrophic Factor; Cell Count; Cell Death; Cell Maturation; Cells; Child; Childhood; Clinical; Clinical Research; Data; Development; Development Plans; Disease; Doctor of Philosophy; Educational workshop; Electrophysiology (science); Embryo; Event; Functional disorder; Funding; Gilles de la Tourette syndrome; Goals; Green Fluorescent Proteins; Growth Factor; Hippocampus (Brain); Human; Hypothalamic structure; In Situ Hybridization; Individual; Intervention; K-Series Research Career Programs; Laboratories; Learning; Limbic System; Link; Measures; Medial; Mediating; Mediator of activation protein; Mental disorders; Mentors; Molecular; Mus; Neonatal; Neuroanatomy; Neurobiology; Neurons; Neurosciences; Neurosciences Research; Neurosecretory Systems; Parvalbumins; Patients; Performance; Phenotype; Population; Prefrontal Cortex; Pregnancy; Pregnant Women; Property; Prosencephalon; Psychiatric therapeutic procedure; Psychiatry; Recruitment Activity; Regulation; Research; Research Proposals; Schizophrenia; Slice; Somatostatin; Staging; Stem cells; Stress; Structure; Survival Analysis; System; Techniques; Time; Training; United States National Institutes of Health; Western Blotting; Work; base; calretinin; career; career development; cholinergic; cingulate cortex; depressive symptoms; design; developmental neurobiology; experience; functional outcomes; gamma-Aminobutyric Acid; in vitro activity; in vivo; inhibitory neuron; interest; knowledge base; mature animal; migration; neurobiological mechanism; neurodevelopment; neuron development; offspring; postnatal; prenatal; prenatal exposure; prenatal stress; programs; promoter; public health relevance; research study; response; septohippocampal; skills; social; symposium; transcription factor

DESCRIPTION (provided by applicant: This application presents a career development award that integrates clinical child and adult psychiatry, animal models of developmental neuroscience, and stress neurobiology. The immediate goal is to create a program investigating the developmental mechanisms of the neurobiological effects of prenatal stress, focused on inhibitory neurons. The long term objective is to contribute to the understanding of early developmental events that contribute to severe childhood and adult psychiatric illness, the pathophysiology that underlies disorders such as schizophrenia and Tourette syndrome, and how interventions can modify early developmental changes. The candidate completed a Ph.D. in neuroscience with individual NIH funding and has now been involved in comprehensive training in clinical and research psychiatry for the past 5 years at the Yale Child Study Center (YCSC) and Department of Psychiatry. This award will provide critical support for the continuation of her integrated research in the YCSC Developmental Neurobiology Laboratory and the transition to an independent career in basic developmental neuroscience within the framework of understanding child and adult psychiatric illness. In the research proposal, an animal model of prenatal stress will be used to study the mechanisms of widespread, persistent effects on CNS structure and function. GABAergic systems will be the focus of the research plan, as patients with schizophrenia and other behavioral disorders linked to prenatal stress in humans have abnormal GABAergic neuron populations. Dr. Stevens will complete the first stage of the research plan on the anatomical effects of prenatal stress on inhibitory neurons with the support of this award and the skills she has developed in her postdoctoral work. She will then go on to make assessments of molecular mechanisms of prenatal stress affecting GABAergic populations both during the embryonic time period and during adult development. Functioning of inhibitory neuronal systems will be examined with behavioral and electrophysiological measures. This experimental work also comprises the career development plan for this candidate to obtain the necessary skills for an independent career in basic neuroscience research that can investigate important questions about the neurodevelopment of mental illness. The candidate has recruited an outstanding group of mentors and advisors that will guide the research plan in design, performance of experiments, and analysis of results. For career development, this mentor and advisor team will continue to support the candidate as she develops an independent laboratory program at the YCSC relevant to the neurodevelopment of mental illness and as she pursues additional training in molecular, behavioral, and electrophysiological techniques through coursework, intensive workshops and national conferences. PUBLIC HEALTH RELEVANCE: At a minimum, this work will address important gaps in the knowledge base regarding the neurodevelopmental basis of conditions related to prenatal stress, including schizophrenia. Broader implications include a more sophisticated understanding of the regulation of inhibitory neuron development and systemic and environmental effects on this regulation. Results of this work will inform child, adolescent and adult psychiatric treatment and the treatment of pregnant women with both pharmacologic and psychotherapeutic interventions.

描述(由申请者提供：本申请颁发职业发展奖，综合临床儿童和成人精神病学、发育神经科学动物模型和应激神经生物学。目前的目标是创建一个项目，研究产前应激对神经生物学影响的发育机制，重点是抑制性神经元。长期目标是帮助了解导致儿童和成人严重精神疾病的早期发育事件、精神分裂症和多发性抽动症等疾病的病理生理基础，以及干预措施如何改变早期发育变化。这位候选人在NIH的个人资助下完成了神经科学博士学位，在过去的5年里，她一直在耶鲁儿童研究中心(YCSC)和精神病学系参与临床和研究精神病学的综合培训。该奖项将为她继续在YCSC发展神经生物学实验室进行综合研究以及在了解儿童和成人精神疾病的框架内过渡到基础发展神经科学的独立职业生涯提供关键支持。在这项研究计划中，将使用产前应激的动物模型来研究对中枢神经系统结构和功能的广泛、持续影响的机制。GABA能系统将是研究计划的重点，因为精神分裂症和其他与人类产前应激有关的行为障碍患者有异常的GABA能神经元群。史蒂文斯博士将在该奖项和她在博士后工作中培养的技能的支持下，完成关于产前应激对抑制性神经元的解剖学影响的研究计划的第一阶段。然后，她将继续评估在胚胎时期和成年发育期间影响GABA能群体的产前应激的分子机制。抑制神经系统的功能将通过行为和电生理措施进行检查。这项实验性工作还包括该候选人的职业发展计划，以获得在基础神经科学研究中独立职业所需的技能，该研究可以调查有关精神疾病神经发育的重要问题。候选人已经招募了一批优秀的导师和顾问，他们将在设计、实验执行和结果分析方面指导研究计划。在职业发展方面，这个导师和顾问团队将继续支持候选人，因为她在基督教青年会开发了一个与精神疾病神经发展相关的独立实验室项目，并通过课程作业、密集研讨会和国家会议寻求分子、行为和电生理技术的额外培训。 公共卫生相关性：至少，这项工作将解决与包括精神分裂症在内的产前应激相关疾病的神经发育基础方面的知识基础方面的重要空白。更广泛的影响包括对抑制神经元发育的调控以及系统和环境对这一调控的影响有更深入的了解。这项工作的结果将为儿童、青少年和成人的精神治疗和孕妇的治疗提供药物和心理治疗干预。