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，定义为子宫内膜腺体和子宫内膜腔外基质的存在。子宫内膜异位症发病的原因尚不清楚，但压力和下丘脑-垂体-肾上腺轴（HPA）功能异常之间的关系已被证实。在这些慢性疾病中，长时间的初始HPA轴激活可能会导致皮质醇减少，这可能是对持续HPA活动的适应性反应。动物环境富集的良好表征模型已被证明可以稳定HPA轴活性。环境富集在人类中共享行为疗法的几个组成部分，使其成为研究其作为慢性疾病（如子宫内膜异位症）补充疗法的合适模型。根据这些先前的发现，我们假设环境丰富，作为行为治疗的一种模式，将减少子宫内膜异位症的症状。这一假设将在两个特定的目标进行测试：第一个目标将使用环境丰富的子宫内膜异位症大鼠模型，以测试是否减少疾病的严重程度，通过HPA轴活动的行为和分子参数测量。目的2包括两个实验，其中第一个将表征子宫内膜异位症进展期间（7天和60天）的HPA轴活性。第二个实验将使用CRFR 1拮抗剂，试图在疾病建立的初始阶段与环境富集结果相比调节HPA轴活性。在拟定研究计划的同时，还设计了一系列活动，以提高候选人的职业发展、教学和课程设置技能。候选人将参加一系列研讨会，重点课程和培训，这将提高她的知识和补充和替代医学（CAM）实践在研究中的适用性。这将最终导致一个CAM为导向的选修课程的整合，提供给医学庞塞学院的研究生，在此期间，候选人可以展示她的研究成果。拟议的职业奖励的预期成果如下1）提供经验数据，导致增加使用行为疗法治疗子宫内膜异位症，2）提高课程建设技能，这将导致CAM课程和产品在Ponce医学院的实施，和3）培训候选人，以实现她作为学术研究人员的独立性，从而获得独立的资金。