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: 10579991
• 负责人: William A. Carlezon
• 金额: $ 264.73万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579991
• 关键词: Animal Model; Anxiety Disorders; Autopsy; Biological; Biology; Brain; Cells; Chemicals; Clinical; Collaborations; Collection; Communication; Communities; Complement; Corticotropin-Releasing Hormone; Data Set; Dedications; Development; Diagnostic; Dimensions; Disease; Education; 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; Training and Education; Translating; Work; antagonist; behavior measurement; career; career development; clinical care; 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 reduction; 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.

总结：备用中心 Silvio O. Conte Center for Stress Peptide Advanced Research，Education，& Dissemination（英语：Conte Center for Stress Peptide Advanced Research，Education，& Dissemination） 姆克林医院将联合收割机在应激生物学领域的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激素）的神经生物学效应， 因子）和PACAP（腺苷酸环化酶激活多肽），这两种肽具有良好的验证作用 压力相关的生物学这些系统中的基因改变使人们更容易受到伤害 对于应激，施用任一肽模拟关键的应激效应，并且两个系统都被应激改变。 它们在不同物种间的高度保守性表明，每种基因的调节作用都同样重要， 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比CRF系统激活的应激效应更持久。 科学元素包括互补的分子、细胞、电路、生理和行为测量 在小鼠和人类，以及详细的假设检验，在死后的大脑样本中获得的， 患有创伤后应激障碍（PTSD）的个体和健康对照。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 项目以及社会媒体方法，以吸引科学家和非专业人士。我们的总体目标是 协同作用的基础，将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 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，作为一种资源， 科学界和其他领域。目标1（合作）是汇集领先的研究人员谁是 致力于了解压力，并通过结合生物学的新见解， 尖端技术，并建立一个框架，使持续合作的服务， 推进发现和创新。目标2（调查）是使用多学科、RDoC兼容的 进行高影响力研究的方法，改变我们对CRF和PACAP的机械理解 系统，以促进改进的诊断和治疗的发展，为一系列的DSM定义的 由压力引起或加剧的疾病。目标3（推广）是实施独特和有影响力的 加强教育，培训和职业发展的方法，为子孙后代的预防- 压力研究者。目标4（创新）是利用信息和互联网技术实现转型 合作、调查和推广，以实现中心相关活动的广泛传播，包括 分享教育材料和战略，灵活传播新闻，提供数据集。 追求这些目标将使SPARED中心成为阐明大脑的独特资源 压力引起的精神障碍的潜在机制，将这些知识转化为临床护理， 传播我们的研究结果的方式，将与专家以及外行产生共鸣。

项目成果

Predicting Fear Extinction in Posttraumatic Stress Disorder.

• DOI: 10.3390/brainsci13081131
• 发表时间: 2023-07-28
• 期刊: Brain sciences
• 影响因子: 3.3

Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety.

• DOI: 10.1038/s41593-018-0151-z
• 发表时间: 2018-06
• 期刊: Nature neuroscience
• 影响因子: 25
• 作者: Dedic N;Kühne C;Jakovcevski M;Hartmann J;Genewsky AJ;Gomes KS;Anderzhanova E;Pöhlmann ML;Chang S;Kolarz A;Vogl AM;Dine J;Metzger MW;Schmid B;Almada RC;Ressler KJ;Wotjak CT;Grinevich V;Chen A;Schmidt MV;Wurst W;Refojo D;Deussing JM
• 通讯作者: Deussing JM

Impact of social dominance hierarchy on PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice.

社会支配等级对 C57BL/6 雄性小鼠杏仁核中 PACAP 表达、皮质酮和行为的影响。

• DOI: 10.1101/2023.05.03.539254
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Meloni,EdwardG;CarlezonJr,WilliamA;Bolshakov,VadimY
• 通讯作者: Bolshakov,VadimY

The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus of male mice.

伴侣FKBP5塑造了雄性小鼠下丘脑室室核中急性应激反应。

• DOI: 10.1038/s41380-021-01044-x
• 发表时间: 2021-07
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Häusl AS;Brix LM;Hartmann J;Pöhlmann ML;Lopez JP;Menegaz D;Brivio E;Engelhardt C;Roeh S;Bajaj T;Rudolph L;Stoffel R;Hafner K;Goss HM;Reul JMHM;Deussing JM;Eder M;Ressler KJ;Gassen NC;Chen A;Schmidt MV
• 通讯作者: Schmidt MV