Wednesday, April 2, 2025
4/2/2025
Role of gestational hypoxia in maternal brain health - PROJECT SUMMARY Gestational sleep apnea affects 26% of pregnant women and is associated with an increased risk of developing perinatal cognitive and psychosocial dysfunction. Recent studies have revealed the long-lasting effects of healthy pregnancy on the structure and function of the maternal brain. Yet, the mechanisms by which gestational hypoxia, a characteristic of gestational sleep apnea, affects the structure and function of the maternal brain during pregnancy and postpartum are poorly understood. My long-term goal is to build an independent academic career focused on immunological mechanisms contributing to pregnancy-associated cognitive deficits, psychosocial dysfunction, and increased dementia risk. This proposal aims to determine the role of proinflammatory responses in gestational hypoxia-induced maternal neurobiological and behavioral changes throughout pregnancy and postpartum. The proposed studies will test the central hypothesis that gestational hypoxia contributes to maternal neuroinflammation, which mediates cognitive and psychosocial dysfunction that persists postpartum. During the mentored phase, we will use a preclinical rat model of gestational sleep apnea-associated intermittent hypoxia to determine the effects of gestational hypoxia on 1) maternal cognitive and psychosocial function during pregnancy (Aim 1) and 2) the contribution of maternal hippocampal proinflammatory responses to neuronal dysfunction using hippocampal-specific knockdown of receptors for the master regulator of proinflammatory responses, TNF-α (Aim 2). The mentored phase will consist of critical training in rodent behavior analyses and advanced neuroanatomical techniques, as well as quarterly meetings with my Advisory Committee and career development experiences that are necessary for transitioning to an independent academic position. In the independent phase (Aim 3), I will determine the effects of gestational hypoxia on long-term neuroinflammation contributing to persistent maternal cognitive and psychosocial dysfunction. Using our rat model of gestational intermittent hypoxia, I will characterize maternal cognitive and psychosocial function alongside maternal brain immune cell activation, polarization, and function through two months post-pregnancy. Furthermore, I will continue to meet with my Advisory Committee throughout the independent phase to ensure success as a junior faculty. Overall, successful completion of the proposed studies will establish the contribution of gestational hypoxia-induced proinflammatory responses to pregnancy-associated cognitive and psychosocial function and will launch my independent academic career focused on maternal brain health throughout the lifespan. I am positioned in the ideal environment for the proposed research and my career development, as my mentors harbor the technical expertise, successful mentoring backgrounds, and established collaborations alongside state-of-the-art resources at UNTHSC. This stimulating academic environment at UNTHSC and commitment of my mentors empower my successful transition to an independent tenure-track academic research position.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).