Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes

生殖衰老健康结果的压力和神经调节中心

• 批准号: 10669188
• 负责人: HADINE JOFFE
• 金额: $ 171.68万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669188
• 关键词: Adrenal Cortex Hormones; Affect; Age; Aging; Animal Model; Animals; Basic Science; Biology; Body fat; Brain; Brain imaging; Cardiovascular Diseases; Clinical; Clinical Sciences; Cognition; Collaborations; Data; Dementia; Dynorphins; Education; Exposure to; Fellowship; Female; Gender; Goals; Gonadal Steroid Hormones; Growth; Health; Heart Diseases; Hormone use; Hospitals; Hot flushes; Human; Impaired cognition; Infrastructure; Institution; Interdisciplinary Study; Investigation; KISS1 gene; Knowledge; Leadership; Link; Longevity; Mediating; Medicine; Metabolic; Metabolic stress; Neurobehavioral Manifestations; Neuroendocrinology; Neurons; Neurosciences; Neurosecretory Systems; Outcome; Perimenopause; Pilot Projects; Policies; Population; Population Sciences; Postmenopause; Predisposition; Pregnancy; Prevention strategy; Process; Psychosocial Stress; Public Health; Quality of life; Research; Research Personnel; Resources; Rodent; Rodent Model; Role; Science; Scientist; Sex Differences; Site; Sleep; Sleep Disorders; Sleep disturbances; Stress; Translational Research; Travel; Woman; Women' s Health; Work; biological adaptation to stress; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; career; cognitive change; dementia risk; experience; gamma-Aminobutyric Acid; gender difference; health difference; hormone therapy; human model; hypothalamic pituitary gonadal axis; improved; innovation; medical schools; middle age; neural; neural circuit; neural network; neuroimaging; neuromechanism; neuropsychiatric symptom; neuroregulation; next generation; novel; novel therapeutics; nutritional epidemiology; older women; physiologic stressor; poor sleep; programs; reproductive epidemiology; reproductive hormone; reproductive senescence; response; sex; social stress; social stressor; stressor; symptom treatment; synergism; translational research program; vasomotor symptoms

Older women experience dramatic changes in the hypothalamic-pituitary-gonadal (HPG) axis and female reproductive hormones, producing vasomotor symptoms (VMS), sleep problems, cognitive changes, and cardiometabolic risks, which increase susceptibility to cardiovascular disease (CVD) and dementia. VMS occur in 85% of women and persist in one-third for 10+ years after menopause, potentially leading to prolonged disruption of quality of life, sleep disturbance, cardiometabolic risk, and extended VMS treatment, conferring further risk for CVD and dementia. Such health outcomes may also be influenced by stress exposures across the lifespan and during pregnancy, which may exert their effects through neural mechanisms. Brigham and Women’s Hospital (BWH) and Harvard Medical School (HMS) seek to establish a SCORE to advance our understanding of stress exposures and neural regulation of reproductive aging health outcomes, and to catalyze growth of translational women’s health and sex-differences research in aging women. We will pursue novel translational science through three Projects: Project 1 (Joffe/Mahon; clinical science) will define evoked stress responsivity, stress-related activation of neural networks on functional brain imaging, and GABA concentrations as markers of VMS occurrence and persistence, including compounding effects of poor sleep and stress exposures. Project 2 (Oken/Chavarro; population science) will determine whether perimenopausal women with higher exposure to social stressors across the lifespan and physiological stressors across pregnancy have greater cardiometabolic risk, sleep, cognitive, and neuropsychiatric symptoms. Project 3 (Kaiser/Navarro; basic science) will characterize the role of kisspeptin, neurokinin, and dynorphin (KNDy) neurons and upstream GABAergic neurons in mediating the effects of stress and corticosteroids on the HPG axis, VMS, and sleep disturbances in a rodent model. These scientific efforts will receive critical support from our Cores: The Sleep Resource Core (Klerman) will extend our scientific impact by investigating sleep outcomes in humans and rodents. The Career Enhancement Core (Rexrode/Rich-Edwards) will promote early- career and new sex-differences investigators by supporting Scholars, Pilot Projects, Travel Exchange Fellowships, and a robust educational program. The Leadership Administrative Core (Joffe/Manson) will provide scientific and administrative oversight and engage with the SCORE Consortium. Building on existing, fruitful collaborations, our outstanding interdisciplinary team of investigators—leaders in women’s health, sleep medicine, neuroimaging, neuroendocrinology, stress science, cognition, cardiometabolic, and reproductive epidemiology—will leverage robust resources at the Connors Center for Women’s Health and Gender Biology and across synergistic women’s health and sleep programs at BWH. This SCORE will produce a significant public health impact by advancing our understanding of the role and mechanisms of stress in producing reproductive aging health outcomes that are linked with CVD and dementia susceptibility in aging women.

老年妇女在下丘脑-垂体-性腺（HPG）轴和女性中经历了巨大的变化