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: 10840078
• 负责人: HADINE JOFFE
• 金额: $ 22.4万
• 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/10840078
• 关键词: Adrenal Cortex Hormones; Aging; Basic Science; Biology; Body fat; Brain; Brain imaging; Cardiovascular Diseases; Clinical Sciences; Cognition; Collaborations; Dementia; Dynorphins; Education; Exposure to; Fellowship; Female; Gender; Growth; Health; Heart Diseases; Hospitals; Hot flushes; Human; KISS1 gene; Knowledge; Leadership; Link; Longevity; Mediating; Medicine; Metabolic stress; Neurobehavioral Manifestations; Neuroendocrinology; Neurons; Outcome; Perimenopause; Pilot Projects; Population Sciences; Postmenopause; Predisposition; Pregnancy; Public Health; Quality of life; Research; Research Personnel; Resources; Rodent; Rodent Model; Role; Science; Sex Differences; Sleep; Sleep Disorders; Sleep disturbances; Stress; Translational Research; Travel; Woman; Women' s Health; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; career; cognitive change; experience; gamma-Aminobutyric Acid; gender difference; health difference; hypothalamic pituitary gonadal axis; medical schools; middle age; neural network; neuroimaging; neuromechanism; neuropsychiatric symptom; neuroregulation; next generation; novel; older women; physiologic stressor; poor sleep; programs; reproductive epidemiology; reproductive hormone; reproductive senescence; response; sex; social stress; social stressor; symptom treatment; 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.

老年女性的下丘脑-垂体-性腺（HPG）轴和女性经历了巨大的变化 生殖激素，产生血管紧张症状（VMS），睡眠问题，认知变化， 心脏代谢风险，增加对心血管疾病（CVD）和痴呆症的易感性。VMS发生 在85%的女性中，三分之一的女性在绝经后持续10年以上，可能导致长期的 生活质量中断、睡眠障碍、心脏代谢风险和VMS治疗延长， 进一步增加心血管疾病和痴呆的风险。这些健康结果也可能受到压力暴露的影响， 在寿命和怀孕期间，这可能通过神经机制发挥其作用。布莱根 妇女医院（BWH）和哈佛医学院（HMS）寻求建立一个SCORE，以推进我们的 了解压力暴露和生殖衰老健康结果的神经调节，并促进 翻译妇女健康和老龄妇女性别差异研究的增长。我们将追求新奇 通过三个项目转化科学：项目1（Joffe/Mahon;临床科学）将定义诱发应激 功能性脑成像中神经网络的反应性、应激相关激活和GABA浓度 作为VMS发生和持续的标志，包括睡眠不良和压力的复合影响 暴露。项目2（Oken/Chavarro;人口科学）将确定患有 在整个生命周期中更高的社会压力和怀孕期间的生理压力， 更大的心脏代谢风险、睡眠、认知和神经精神症状。项目3（Kaiser/Navarro;基本 科学）将表征kisspeptin，神经激肽和强啡肽（KNDy）神经元和上游的作用 GABA能神经元介导应激和皮质类固醇对HPG轴、VMS和睡眠的影响 啮齿动物模型中的干扰。这些科学努力将得到我们的核心的关键支持：睡眠 资源核心（Klerman）将通过调查人类的睡眠结果来扩大我们的科学影响， 啮齿动物职业提升核心（Rexrode/Rich-Edwards）将促进早期职业和新性别- 通过支持学者，试点项目，旅游交流奖学金和强大的差异调查 教育计划。领导管理核心（Joffe/曼森）将提供科学和 行政监督，并与SCORE联盟合作。在现有的富有成效的合作基础上， 我们杰出的跨学科团队，包括女性健康，睡眠医学， 神经影像学、神经内分泌学、应激科学、认知、心脏代谢和生殖流行病学- 将利用康纳斯妇女健康和性别生物学中心的强大资源， BWH的协同妇女健康和睡眠计划。这一评分将产生重大的公共卫生 通过推进我们对压力在产生生殖衰老中的作用和机制的理解， 健康结果与老年妇女的心血管疾病和痴呆易感性有关。