Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes

老年女性的下丘脑-垂体-性腺(HPG)轴和女性 生殖激素，产生血管运动症状(VMS)，睡眠问题，认知变化，以及 心脏代谢风险，增加心血管疾病(CVD)和痴呆症的易感性。发生VMS 在85%的女性中，绝经后三分之一的人持续10年以上，可能会导致延长 生活质量中断、睡眠障碍、心脏代谢风险和延长VMS治疗时间 进一步增加患心血管疾病和痴呆症的风险。这样的健康结果也可能受到压力暴露的影响 寿命和妊娠期，这可能通过神经机制发挥作用。布里格姆和 妇女医院(BWH)和哈佛医学院(HMS)寻求建立一个分数来推进我们的 了解应激暴露和生殖衰老健康结局的神经调节，并催化 翻译女性健康成长与老年女性性别差异研究。我们将追求新奇 翻译科学通过三个项目：项目1(Joffe/Mahon；临床科学)将定义诱发应激 神经网络对脑功能成像的响应性、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 曝光。项目2(Oken/Chavarro；人口科学)将确定围绝经期妇女是否患有 一生中较高的社会压力暴露和怀孕期间较高的生理压力 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Kispeptin、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糖皮质激素对HPG轴、VMS和睡眠的影响 啮齿动物模型中的骚乱。这些科学努力将得到我们核心的关键支持：睡眠 资源核心(Klerman)将通过调查人类和 啮齿动物。职业提升核心(力士乐/Rich-Edwards)将促进职业生涯早期和新的性行为- 通过支持学者、试点项目、旅行交流奖学金和稳健的 教育项目。领导行政核心(约菲/曼森)将提供科学和 行政监督，并与SCORE联盟接触。建立在现有的、富有成效的合作基础上， 我们杰出的跨学科研究团队-妇女健康、睡眠医学、 神经成像、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以及其他机构的强大资源 BWH的妇女健康和睡眠计划的协同。这一成绩将产生重大的公共卫生 通过提高我们对压力在导致生殖衰老中的作用和机制的理解而产生的影响 与老年妇女的心血管疾病和痴呆症易感性有关的健康结果。

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.