Silvio O. Conte Center for Stress Peptide Advanced Research, Education, & Dissemination (SPARED) at McLean Hospital

Silvio O. Conte 应激肽高级研究、教育中心，

• 批准号: 10116474
• 负责人: William A. Carlezon
• 金额: $ 271.61万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116474
• 关键词: Animal Model; Anxiety Disorders; Autopsy; Biological; Biology; Brain; Cells; Chemicals; Clinical; Collaborations; Collection; Communication; Communities; Complement; Corticotropin-Releasing Hormone; Data Set; Development; Diagnostic; Dimensions; Disease; Education; Education and Outreach; Educational Activities; Educational Materials; Elements; Future Generations; Goals; Growth; Health; Hospitals; Human; Individual; Internet; Investigation; Knowledge; Learning; Mental disorders; Molecular; Mood Disorders; Mus; Mutation; Neurobiology; Pathologic; Pathway interactions; Peptides; Persons; Phenotype; Physiological; Post-Traumatic Stress Disorders; Research; Research Domain Criteria; Research Personnel; Resources; Role; Sampling; Science; Scientist; Services; Stress; System; Technology; Testing; Therapeutic; Training Activity; Training and Education; Translating; Work; base; behavior measurement; career; career development; clinical care; cohesion; digital; improved; innovation; insight; interest; multidisciplinary; news; novel therapeutic intervention; novel therapeutics; outreach; outreach program; peptidomimetics; pituitary adenylate cyclase activating polypeptide; pre-clinical; precision medicine; response; social media; stress related disorder; synergism; web site

SUMMARY: SPARED CENTER The Silvio O. Conte Center for Stress Peptide Advanced Research, Education, & Dissemination (SPARED) at McLean Hospital will combine world-renowned preclinical and clinical researchers in the field of stress biology to comprehensively examine, compare, and contrast the neurobiological effects of CRF (Corticotropin-Releasing Factor) and PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide), two peptides with well-validated roles in the biology of stress-related conditions. Genetic alterations in these systems render people more vulnerable to stress, administration of either peptide mimics key stress effects, and both systems are altered by stress. Their high degree of conservation across species suggests that each regulates equally important—yet subtly different—aspects of stress responsiveness. Indeed, a major difference revealed by animal models is that the stressful effects of PACAP system activation tend to be more persistent than those of CRF system activation. The scientific elements include complementary molecular, cellular, circuit, physiologic, and behavioral measures in mice and humans, as well as detailed hypothesis testing in postmortem brain samples obtained from individuals with Post-Traumatic Stress Disorder (PTSD) and healthy controls. To complement the science, the Center will also support a broad range of training and educational activities, including expansion of outreach programs as well as social media approaches to engage scientists and lay-persons. Our overall Aims provide the basis for synergy that will transform this work from a collection of individual projects into a cohesive Center where each element enriches, and is enriched by, the activities of the others, serving as a resource that benefits the scientific community and beyond. Aim 1 (Collaboration) is to bring together leading researchers who are committed to understanding stress and reducing its health burdens by combining new insights on biology with cutting-edge technologies, and establish a framework that enables sustained collaboration in the service of advancing discovery and innovation. Aim 2 (Investigation) is to use a multidisciplinary, RDoC-compatible approach to conduct high-impact research that transforms our mechanistic understanding of CRF and PACAP systems to facilitate the development of improved diagnostics and therapeutics for a range of DSM-defined disorders that are caused or exacerbated by stress. Aim 3 (Outreach) is to implement unique and impactful approaches that enhance education, training, and career development for future generations of translationally- oriented stress researchers. Aim 4 (Innovation) is to use information and internet technologies to transform collaboration, investigation, and outreach to achieve broad communication of Center-related activities, including sharing of educational materials and strategies, nimbly disseminating news, and making available data sets. Pursuit of these goals will establish the SPARED Center as a unique resource for elucidating the brain mechanisms underlying stress-induced psychiatric disorders, translating this knowledge to clinical care, and disseminating our findings in ways that will resonate with experts as well as the lay-public.

摘要：幸存的中心 Silvio O. Conte 应激肽高级研究、教育和传播中心 (SPARED)，位于 麦克莱恩医院将联合应激生物学领域世界知名的临床前和临床研究人员 全面检查、比较和对比 CRF（促肾上腺皮质激素释放）的神经生物学效应 因子）和 PACAP（垂体腺苷酸环化酶激活多肽），两种具有充分验证作用的肽 在与压力相关的条件的生物学中。这些系统的基因改变使人们更加脆弱 对于压力，任何一种肽的施用都会模拟关键的压力效应，并且这两个系统都会因压力而改变。 它们在不同物种之间的高度保护表明，每个物种的调节同样重要——但微妙 压力反应的不同方面。事实上，动物模型揭示的一个主要区别是 PACAP 系统激活的压力效应往往比 CRF 系统激活的压力效应更持久。 科学要素包括互补的分子、细胞、电路、生理和行为测量 在小鼠和人类中，以及从死后大脑样本中获得的详细假设检验 患有创伤后应激障碍（PTSD）的人和健康对照者。为了补充科学， 中心还将支持广泛的培训和教育活动，包括扩大外展范围 项目以及社交媒体方法来吸引科学家和非专业人士的参与。我们的总体目标提供 协同作用的基础，将把这项工作从单个项目的集合转变为一个有凝聚力的中心 其中每个要素都丰富了其他要素的活动，并被其他要素的活动所丰富，成为造福人类的资源 科学界及其他领域。目标 1（合作）是将以下领域的领先研究人员聚集在一起 致力于通过将生物学的新见解与 尖端技术，并建立一个能够持续合作的框架 推进发现和创新。目标 2（调查）是使用多学科、RDoC 兼容的方法 进行高影响力研究的方法，改变我们对 CRF 和 PACAP 的机制理解 系统，以促进针对一系列 DSM 定义的改进诊断和治疗的开发 由压力引起或加剧的疾病。目标 3（外展）是实施独特且有影响力的 加强未来几代转化者的教育、培训和职业发展的方法 面向压力研究人员。目标4（创新）是利用信息和互联网技术进行变革 协作、调查和外展，以实现中心相关活动的广泛沟通，包括 共享教育材料和策略、灵活传播新闻并提供可用的数据集。 追求这些目标将使 SPARED 中心成为阐明大脑的独特资源 压力诱发精神疾病的机制，将这些知识转化为临床护理，以及 以引起专家和公众共鸣的方式传播我们的研究结果。