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: 9904765
• 负责人: William A. Carlezon
• 金额: $ 269.1万
• 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/9904765
• 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：备用中心 西尔维奥·O·孔特应激肽高级研究、教育和传播中心(备用)： McLean医院将结合世界知名的应激生物学领域的临床前和临床研究人员 全面检测、比较和对比促肾上腺皮质激素释放的神经生物学效应 因子)和PACAP(垂体腺苷环化酶激活多肽)，这两种多肽的作用得到了很好的验证 在与压力相关的条件的生物学中。这些系统中的基因改变使人们更容易受到伤害 对于应激，两种多肽中的任何一种都会模拟关键的应激效应，而这两个系统都会因应激而改变。 它们在不同物种之间的高度保守性表明，每一种都同样重要-但微妙地 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系统激活的应激效应往往比CRF系统激活的更持久。 科学要素包括互补的分子、细胞、回路、生理和行为测量。 在小鼠和人类身上，以及在死后大脑样本中进行详细的假设检验 创伤后应激障碍(PTSD)患者和健康对照组。为了补充科学， 中心还将支持广泛的培训和教育活动，包括扩大外联活动。 项目以及社交媒体方法，以吸引科学家和非专业人士。我们的总体目标是 协同的基础将把这项工作从一个单独的项目集合转变为一个有凝聚力的中心 在这里，每个元素都丰富了其他元素的活动，并被其他元素的活动所丰富，成为一种有益的资源 科学界和更远的地方。目标1(协作)是将具有以下特点的领先研究人员聚集在一起 致力于通过结合生物学的新见解来理解压力并减轻其健康负担 尖端技术，并建立一个框架，使之能够在服务于 推进发现和创新。目标2(调查)是使用与RDoC兼容的多学科 进行高影响力研究的方法，改变我们对CRF和PACAP的机械理解 促进开发针对一系列DSM定义的改进的诊断和治疗方法的系统 由压力引起或加剧的紊乱。目标3(推广)是实施独特和有影响力的 加强未来几代人的教育、培训和职业发展的方法- 有针对性的压力研究人员。目标4(创新)是利用信息和互联网技术实现 协作、调查和外展，以实现与中心相关活动的广泛沟通，包括 共享教育材料和战略，灵活传播新闻，并提供可用的数据集。 对这些目标的追求将使备用中心成为阐明大脑的独特资源 应激诱发精神障碍的潜在机制，将这一知识转化为临床护理，以及 以能引起专家和公众共鸣的方式传播我们的调查结果。