Neuro HPA Project 1

项目1：摘要 性激素在设定免疫反应的基调方面具有影响力，雌二醇表现出特别重要的作用。 在女性的整个生命周期中都有很大的影响。虽然主要是抗炎和保护， 雌二醇可能具有不同的作用。此外，雌二醇的影响和可用性随着年龄的增长而变化， 尤其是在更年期此外，暴露于压力源可以影响功能， 性激素包括雌二醇感染艾滋病毒的妇女（WLH）可能更容易受到以下因素的影响： 应激和创伤暴露对激素功能的影响和突然的变化可能表现为增强 炎症信号拟议中的研究将进一步加深我们对衰老生物学的理解， 特别是WLH的预后，并表征免疫衰老和 内分泌衰老计划中的研究将确定雌激素缺乏症在全身和受体 水平和评估这些参数的整体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过度觉醒， 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，我们将描述创伤暴露和雌激素受体功能对 WLH中分子水平的炎症。总的来说，本提案产生的数据将提供关键的 关于雌二醇信号传导对WLH炎症影响的信息，并提供机制见解 更广泛地研究雌二醇受体功能对炎症的影响。因为创伤暴露和 其相关的不良心理健康结果（即创伤后应激障碍; PTSD）在以下方面控制不良： WLH和PTSD对HIV的发病和传播有着危险的影响，它具有至关重要的意义 确定创伤和PTSD与HIV共病的影响，以确定最有效的治疗方法， 这一复杂的合作伙伴关系。

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.