Emory Specialized Center of Research Excellence (SCORE) on Sex Differences

Emory University, Atlanta GA

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY / ABSTRACT – Project 2 (Brain) 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 and the influence and availability of estradiol changes with aging, most notably with the menopause transition. Furthermore, exposure to stressors such as trauma can impact the functions of sex hormones, including estradiol, as well as contribute to systemic inflammation through gut barrier dysfunction and reduced microbiota diversity. Project 2 will address the overarching hypothesis that PTSD and menopause interact to precipitate alterations in the brain, bone, and heart that are associated with alterations in ER function and peripheral inflammation secondary to gut dysfunction and dysbiosis. We will assess the interactions among neuroendocrine regulatory interactions with ‘leaky gut metrics’ and general systemic inflammation, and risk for acceleration of adverse effects on bone, brain, and heart health. The planned research will evaluate the associations among estrogen receptor expression and ex vivo anti- inflammatory actions with peripheral cytokines, gut barrier dysfunction, reduced gut microbiota species, and markers of brain health, including circulating neurofilament light chain and cognitive function, across the menopause transition. We will also conduct clinical interviews to assess trauma exposure and PTSD to examine how these psychosocial factors interact with social support to exacerbate and mitigate estrogen deficiency and inflammation on negative outcomes in end organ systems including changes in cognition (Project 2: Brain), bone mineral density (Project 1: Bone) and endothelial dysfunction, arterial stiffness, and coronary atherosclerosis (Project 3: Heart) from Cycle 1 to Cycle 2 of the Emory SCORE. Overall, our studies will increase our understanding of the protective role of social support in prevention of inflammation-related, non-AIDS age-related comorbidities (NACMs) in a highly trauma-exposed group of women living with HIV and at risk for HIV and provide foundational knowledge describing the interaction of trauma history and reproductive senescence on multi-system aging that may have implications for understanding interactions in multiple diseases and disorders beyond the study of HIV.