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; 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：不保留中心 Silvio O. Conte应激肽中心高级研究，教育和传播（遗漏） 麦克莱恩医院将在压力生物学领域结合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的神经生物学效应（皮质激素释放） 因子）和PACAP（垂体腺苷酸环化酶激活多肽），两个具有验证作用的宠物 在与压力相关条件的生物学中。这些系统中的遗传改变使人们更脆弱 为了压力，给予任何一种肽模拟关键应力效应，并且两个系统都会因应力而改变。 它们跨物种的高度保护表明，每个物种都同样重要 - 但微妙 不同的 - 压力反应能力。确实，动物模型揭示的主要区别在于 与CRF系统激活相比，PACAP系统激活的压力效应往往更持久。 科学元素包括完整的分子，细胞，电路，生理和行为测量 在小鼠和人类中，以及从从中获得的详细假设检验 具有创伤后应激障碍（PTSD）和健康对照的人。为了完成科学， 中心还将支持广泛的培训和教育活动，包括扩展外展活动 计划以及社交媒体的方法来吸引科学家和外行者。我们的整体目标提供 协同作用的基础将将这项工作从一系列单个项目转变为凝聚力中心 每个元素都充实并丰富了其他元素的活动，作为一种受益的资源 科学界及以后。 AIM 1（协作）是将领先的研究人员聚集在一起 致力于理解压力并通过将生物学的新见解与 尖端技术，并建立一个框架，以实现持续的协作 推进发现和创新。 AIM 2（调查）是使用多学科，兼容RDOC 进行高影响研究的方法，可以改变我们对CRF和PACAP的机械理解 促进一系列DSM定义的改进诊断和疗法的开发系统 压力引起或加剧的疾病。目标3（外展）是实施独特而有影响力的 为子孙后代的翻译而增强教育，培训和职业发展的方法 定向压力研究人员。 AIM 4（创新）是使用信息和互联网技术来转换 协作，调查和宣传，以实现与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数据集。 追求这些目标将建立不幸的中心作为阐明大脑的独特资源 压力引起的精神疾病的基础机制，将这些知识转化为临床护理，并 以与专家以及外行公共的共鸣的方式传播我们的发现。