Mechanisms of HPA axis alterations during the development of endometriosis

子宫内膜异位症发生过程中HPA轴改变的机制

• 批准号: 9023430
• 负责人: ANNELYN TORRES-REVERON
• 金额: $ 14.31万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9023430
• 关键词: Alternative Therapies; Animal Model; Animals; Anxiety; Award; Behavior; Behavior Therapy; Behavioral; Brain; CRF receptor type 1; Chronic; Chronic Fatigue Syndrome; Cognitive Therapy; Complementary and alternative medicine; Complementary therapies; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Corticotropin-Releasing Hormone Receptors; Data; Development; Diagnosis; Disease; Disease Progression; Dysmenorrhea; Educational Curriculum; Educational process of instructing; Endocrine system; Endometrial; Endometrium; Environment; Feedback; Funding; Gland; Glucocorticoids; Health; Human; Hydrocortisone; Immune response; Immune system; Individual; Infertility; Inflammation; Inflammatory; Inflammatory Response; Intervention; Irritable Bowel Syndrome; Knowledge; Lead; Light; Measures; Medical Research; Methods; Modeling; Modification; Molecular; Neurosecretory Systems; Operative Surgical Procedures; Outcome; Patients; Peritoneal; Peritoneal Fluid; Phase; Plasma; Productivity; Psychological Stress; Public Health; Quality of life; Rattus; Reproductive system; Research; Research Personnel; Salivary; Series; Severities; Severity of illness; Signal Transduction; Stress; Symptoms; System; Testing; Therapeutic; Training; Uterine cavity; Vesicle; Woman; Work; alternative treatment; antalarmin; base; behavior measurement; career; career development; chronic pelvic pain; design; endometriosis; environmental enrichment for laboratory animals; graduate student; hypothalamic-pituitary-adrenal axis; improved; inhibitor/antagonist; medical schools; psychologic; reduce symptoms; research in practice; research study; response; skills; success; symptomatology

DESCRIPTION (provided by applicant): Endometriosis is a chronic inflammatory disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity. The causes of endometriosis onset are still unknown, but a relationship between stress and abnormal functioning of the hypothalamic-pituitary-adrenal axis (HPA) has been documented. In these chronic conditions, prolonged periods of initial HPA axis activation might be followed by a state of hypocortisolism, which might result as an adaptive response to sustained HPA activity. The well-characterized model of animal environmental enrichment has been proven to stabilize HPA axis activity. Environmental enrichment shares several components of behavioral therapies in humans making it a suitable model to study its use as complementary therapy for chronic conditions such as endometriosis. In light of these previous findings, we hypothesize that environmental enrichment, as a model of behavioral therapy, will reduce the symptoms of endometriosis. This hypothesis will be tested in two specific aims: The first aim will use environmental enrichment in the rat model of endometriosis to test whether the severity of the disease is diminished as measured by behavioral and molecular parameters of HPA axis activity. Aim 2 consists of two experiments where the first one will characterize the HPA axis activity during the progression (7 and 60 days) of endometriosis. The second experiment will use a CRFR1 antagonist to attempt to regulate HPA axis activity during the initial phases of the disease establishment in comparison to environmental enrichment outcomes. In parallel to the proposed research plan, a series of activities have been designed to enhance the candidate's career development, teaching and curriculum building skills. The candidate will participate in a series of seminars, focused courses and training that will enhance her knowledge and applicability of complementary and alternative medicine (CAM) practices in research. This will ultimately lead to the integration of a CAM-oriented elective course to be offered to graduate students from Ponce School of Medicine during which the candidate can showcase her research findings. The expected outcomes of the proposed career award are the following 1) Provide empirical data leading towards the increased use of behavioral therapy for endometriosis treatment, 2) Improve curriculum building skills that will lead towards the implementation of CAM course and offerings at Ponce School of Medicine, and 3) Train the candidate to achieve her independence as an academic researcher leading towards obtaining independent funding.

描述（由申请人提供）：子宫内膜异位症是一种慢性炎症性疾病，定义为子宫内膜腔外的子宫内膜腺和基质。子宫内膜异位症发作的原因仍然未知，但是已记录了下丘脑 - 垂体 - 肾上腺轴（HPA）的压力与异常功能之间的关系。在这些慢性条件下，最初的HPA轴激活的延长时期可能是低皮质溶液的状态，这可能是对持续HPA活性的适应性反应。被证明是稳定HPA轴活动的动物环境富集模型。环境富集在人类中具有多种行为疗法的组成部分，使其成为研究其用作子宫内膜异位症等慢性疾病的补充疗法的合适模型。鉴于这些先前的发现，我们假设环境富集是行为疗法的模​​型，将减少子宫内膜异位症的症状。该假设将以两个具体的目的进行检验：第一个目的将使用子宫内膜异位症大鼠模型中的环境富集来测试该疾病的严重程度是否通过通过HPA轴活动的行为和分子参数来测量的疾病的严重程度。 AIM 2由两个实验组成，其中第一个实验将在子宫内膜异位症的进展（7和60天）中表征HPA轴活动。第二个实验将使用CRFR1拮抗剂与环境富集结局相比，试图在疾病建立的初始阶段试图调节HPA轴活动。与拟议的研究计划并行，一系列活动旨在提高候选人的职业发展，教学和课程建设技能。候选人将参加一系列研讨会，集中的课程和培训，以增强她在研究中的互补和替代医学（CAM）实践的知识和适用性。这最终将导致将面向凸轮的选修课程整合给Ponce医学院的研究生，在此期间，候选人可以展示她的研究结果。拟议职业奖的预期结果是以下1）提供经验数据，以增加行为疗法用于子宫内膜异位症治疗的使用，2）提高课程建设技能，这将导致Ponce医学院的CAM课程和产品的实施，以及3）培训候选人作为获得独立资助的候选人的独立性。