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Role of gestational hypoxia in maternal brain health

Award Number: K99HD115156
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/01/2025
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $117,226 )
2026	2026	THE UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Child Health and Human Development Extramural Research	000	2	3/2/2026	NON-COMPETING CONTINUATION	$117,226
														Subtotal = $117,226

Issue Date FY: 2025 ( Subtotal = $117,226 )
2025	2025	THE UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Child Health and Human Development Extramural Research	000	1	2/19/2025	NEW	$117,226
														Subtotal = $117,226

Grand Total All Awards = $234,452

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Role of gestational hypoxia in maternal brain health

Award Number: K99HD115156

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/01/2025

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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