Neuro HPA Project 1

神经 HPA 项目 1

• 批准号: 10459328
• 负责人: Vasiliki Michopoulos
• 金额: $ 28.94万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10459328
• 关键词: Address; Age; Aging; Anti-Inflammatory Agents; Attention; Biology of Aging; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Cells; Centers of Research Excellence; Characteristics; Chronic; Chronic Disease; Clinical; Complex; Consequences of HIV; Dangerousness; Data; Dementia; Development; Disease; Endocrine; Endocrine system; Epidemic; Estradiol; Estradiol Receptors; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Estrogens; Exhibits; Exposure to; Generations; Gonadal Steroid Hormones; HIV; Health; Hormones; Immune response; Immune system; Individual; Inflammation; Inflammatory; Influentials; Interview; Knowledge; Life Cycle Stages; Ligands; Link; Longevity; Malignant Neoplasms; Mediating; Mediation; Mediator of activation protein; Menopause; Mental Health; Modification; Molecular; Musculoskeletal; Nature; Non-Insulin-Dependent Diabetes Mellitus; Organ; Outcome; Pathogenesis; Pathway interactions; Peripheral Blood Mononuclear Cell; Post-Traumatic Stress Disorders; Prevalence; Prognosis; Psychopathology; Psychophysiology; Recording of previous events; Research; Resolution; Risk; Role; Sampling; Sex Differences; Signal Transduction; Specialized Center; Steroid Receptors; Stress; Therapeutic; Tissues; Trauma; Variant; Woman; antiretroviral therapy; comorbidity; cytokine; design; effective therapy; immune activation; immune system function; immunosenescence; insight; mortality; receptor; receptor function; reproductive senescence; stressor; systemic inflammatory response; transmission process; trauma exposure

PROJECT 1: ABSTRACT Sex hormones are influential in setting the tone of immune responses and estradiol exhibits a particularly strong influence that varies across the life cycle in women. Although largely anti-inflammatory and protective, estradiol can have divergent effects. In addition, the influence and availability of estradiol changes with aging, most notably with the menopause transition. Furthermore, exposure to stressors can impact the functions of sex hormones, including estradiol. Women living with HIV (WLH) may be more vulnerable to the effects of stress and trauma exposure on hormone function and precipitated changes may manifest as enhanced inflammatory signaling. The proposed studies will further our understanding of the biology of aging, and specifically the prognosis of WLH, and characterize the link between immunosenescence and endocrinesenescence. The planned research will define estrogen deficiency at both the systemic and receptor level and evaluate the extent to which global variation in these parameters predicts pro-inflammatory pathways in WLH. We will conduct clinical interviews to assess trauma exposure and trauma-related hyperarousal to examine how these factors interact with HIV to exacerbate estrogen deficiency and inflammation. Furthermore, we will characterize the influence of trauma exposure and estrogen receptor function on inflammation at the molecular level in WLH. Overall, the data generated from this proposal will provide critical information about the influence of estradiol signaling on inflammation in WLH and provide mechanistic insight more broadly into the influence of estradiol receptor function on inflammation. Because trauma exposure and its related adverse mental health outcomes (i.e. posttraumatic stress disorder; PTSD) are poorly controlled in WLH, and PTSD has dangerous implications for HIV pathogenesis and transmission, it is of critical importance to identify the effects of trauma and PTSD comorbidity with HIV in order to titrate the most effective treatment approaches for this complex comorbidity.

项目1：摘要 性激素对设定免疫反应的基调有影响，而雌二醇表现出特别的 在女性的整个生命周期中具有不同的强大影响力。尽管在很大程度上是消炎和保护， 雌二醇会产生不同的影响。此外，雌二醇的影响和可利用性随着年龄的增长而变化， 最值得注意的是更年期的过渡。此外，暴露在压力源下可能会影响 性激素，包括雌二醇。携带艾滋病毒的妇女可能更容易受到 应激和创伤暴露对激素功能和突发性变化的影响可能表现为增强 炎症信号。拟议的研究将加深我们对衰老生物学的理解，以及 特别是白斑黄体生成素的预后，并表征免疫衰老和 内分泌衰老。这项计划中的研究将从全身和受体两个方面定义雌激素缺乏。 水平和评估这些参数的全局变化预测促炎途径的程度 在WLH。我们将进行临床访谈，以评估创伤暴露和创伤相关的高度觉醒 研究这些因素如何与艾滋病毒相互作用，加剧雌激素缺乏和炎症。 此外，我们将表征创伤暴露和雌激素受体功能对 白斑黄体细胞在分子水平上的炎症反应。总体而言，根据该提案生成的数据将提供关键的 雌二醇信号对白斑黄体生成素炎症反应影响的信息并提供机制洞察力 更广泛地探讨雌激素受体功能对炎症的影响。因为创伤暴露和 与其相关的不良心理健康后果(即创伤后应激障碍；PTSD)在 和创伤后应激障碍对艾滋病毒的发病和传播具有危险的影响，这是至关重要的 确定创伤和创伤后应激障碍与HIV共病的影响，以确定最有效的治疗方法 治疗这种复杂合并症的方法。