Neuro HPA Project 1

神经 HPA 项目 1

• 批准号: 9790912
• 负责人: Vasiliki Michopoulos
• 金额: $ 29.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9790912
• 关键词: Address; Age; Aging; Anti-inflammatory; Attention; Biology of Aging; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Cells; Centers of Research Excellence; Characteristics; Chronic; Chronic Disease; Clinical; Comorbidity; 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; Psychopathology; Psychophysiology; Recording of previous events; Research; Resolution; Risk; Role; Sampling; Sex Differences; Sex Functioning; Signal Transduction; Specialized Center; Steroid Receptors; Stress; Therapeutic; Tissues; Trauma; Variant; Woman; antiretroviral therapy; cytokine; design; effective therapy; immune activation; immune system function; immunosenescence; insight; mortality; outcome forecast; receptor; receptor function; reproductive senescence; stressor; 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.

项目一：摘要