Estrogen's Neuroprotective Effects on the Brain-Barrier in Restrictive Eating Disorders

雌激素对限制性饮食障碍脑屏障的神经保护作用

• 批准号: 10525278
• 负责人: Lauren Breithaupt
• 金额: $ 18.95万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525278
• 关键词: Adolescence; Adolescent; Anti-Inflammatory Agents; Antiinflammatory Effect; Area; Autoimmune Diseases; Autopsy; Blood; Brain; Brain imaging; Clinical; Competence; Data; Development; Development Plans; Eating Disorders; Estrogen Replacements; Estrogens; Female; Funding; Goals; Gonadal Steroid Hormones; Grant; Hormones; Image; Immune; Immune System Diseases; Immunology; Individual; Infection; Inflammation; Inflammatory; K-Series Research Career Programs; Knowledge; Link; Magnetic Resonance Imaging; Maps; Measurable; Measures; Mediating; Mental disorders; Mentors; Mentorship; Multimodal Imaging; National Institute of Mental Health; Neuraxis; Neurosciences; Outcome; Pathology; Perfusion; Peripheral; Permeability; Physiological; Placebos; Plasma; Population; Production; Proteins; Proteomics; Psychoneuroimmunology; Randomized Controlled Trials; Reaction; Relapse; Research; Risk; Sampling; Shapes; Structure of choroid plexus; Symptoms; Testing; Training; Water; Weight; Work; brain parenchyma; career; career development; epidemiology study; extracellular; healthy weight; immune function; improved; in vivo; inflammatory marker; innovation; neuroimaging; neuroinflammation; new therapeutic target; non-invasive imaging; novel; novel therapeutics; patient oriented research; perfusion imaging; programs; protein expression; restrictive eating; therapeutic target; translational neuroscience; translational scientist

PROJECT SUMMARY/ABSTRACT Restrictive eating disorders (R-EDs) are among the most lethal psychiatric illnesses and common in adolescence. The proposed K23 resubmission will increase our understanding of the brain barrier in R-EDs and test a novel therapeutic target (estrogen) as a neuroprotective moderator of brain barrier functioning, ultimately leading to improved clinical outcomes in R-EDs. My epidemiological research demonstrates that widespread immune dysregulation is prevalent in R-EDs. Estrogen deficiency is common in R-EDs (~60%) and may drive neuroinflammation in R-EDs due to the neuroprotective effects of estrogen on the brain barrier. It remains unclear whether central nervous system (CNS) inflammation (e.g., neuroinflammation) is present in R- EDs, and whether therapy directed at a novel CNS target has beneficial effects on inflammation in R-EDs This K23-Patient Oriented Research Career Development award application uses an innovate translational neuroscience approach to examine the impact of estrogen deficiency and replacement on inflammation, brain- barrier functioning, and core symptoms of R-EDs. By leveraging an ongoing R01 investigating the clinical utility of 12-weeks of estrogen replacement in hypoestrogenemic females with R-EDs, we will evaluate the influence of estrogen replacement (vs. placebo) on inflammation markers (Aim 1), the brain barrier – measured using non-invasive neuroimaging to characterize volume, perfusion, and brain parenchyma extracellular water (Aim 2), and core eating disorder symptoms (Aim 3). The training aim corresponding to this project will support Dr. Lauren Breithaupt in becoming an independent translational scientist with a program of research examining neuroinflammation in eating disorders to identify novel therapeutic treatment targets. Each aim of the study corresponds to a specific training goal, which will map onto three main areas of competency for Dr. Breithaupt : (1) advanced clinical neuroscience principles, (2) non-invasive imaging of brain barrier functioning, and (3) psychoneuroimmunology. Training goals will be implemented under the guidance of Drs. Kamryn Eddy (primary mentor), Marek Kubicki and Madhusmita Misra (co-mentors), Cynthia Bulik, Marco Loggia, Steven Arnold, David Alsop, Beth Stevens, (scientific advisors), and Diego Pizzagalli (collaborator).

项目摘要/摘要 限制性饮食失调（R-ED）是最致命的精神病疾病之一，很常见 青少年。拟议的K23重新提交将增加我们对R-ED中脑屏障的理解 并测试一个新型的热靶（雌激素）作为脑屏障功能的神经保护主持人， 最终导致R-EDS的临床结果改善。我的流行病学研究表明 宽度免疫失调在R-ED中普遍存在。雌激素缺乏在R-ED（约60％）中很常见，并且 由于雌激素对脑屏障的神经保护作用，可能会驱动R-EDS的神经炎症。 尚不清楚中枢神经系统（CNS）注射（例如，神经炎症）是否存在于R-中 EDS以及针对新型CNS靶标的治疗是否对R-ED的注射有益影响 K23患者面向研究职业发展奖应用程序使用创新的翻译 神经科学方法检查雌激素缺乏和替代对感染，脑的影响 R-ED的障碍功能和核心症状。通过利用正在进行的R01调查临床实用程序 在低雌激素的女性中，用R-EDS替代了12周的雌激素，我们将评估影响 在炎症标记（AIM 1）上的雌激素替代（与安慰剂）的脑屏障 - 使用 非侵入性神经影像学表征体积，灌注和脑实质外水（AIM） 2）和核心饮食失调症状（AIM 3）。与该项目相对应的培训目标将支持博士。 Lauren Breithaupt成为一名独立的转化科学家，并进行了研究计划 饮食失调中的神经炎症，以鉴定新的治疗治疗靶标。研究的每个目标 对应于特定的培训目标，该目标将映射到Breithaupt博士的三个主要能力领域： （1）先进的临床神经科学原理，（2）脑屏障功能的非侵入性成像和（3） Psychoneuromumumumumanology。培训目标将在DRS的指导下实施。卡姆林·埃迪（Kamryn Eddy） （小学导师），Marek Kubicki和Madhusmita Misra（联合主管），Cynthia Bulik，Marco Loggia，Steven Arnold，David Allsop，Beth Stevens（科学顾问）和Diego Pizzagalli（合作者）。