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 促进翻译女性健康和老年女性性别差异研究的发展。我们将继续追查 通过三个项目的新的翻译科学：项目1(Joffe/Mahon；临床科学)将定义Evoked 应激反应、应激相关神经网络对脑功能成像的激活，以及GABA 浓度作为VMS发生和持续的标志，包括睡眠不佳的复合效应 以及压力暴露。项目2(Oken/Chavarro；人口科学)将确定围绝经期 女性一生中暴露在社会压力源和生理压力源中的比例更高 怀孕有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；基础科学)将描述Kispeptin、神经激肽和强啡肽(KNDy)的作用 神经元及其上游GABA能神经元参与应激和糖皮质激素对HPG的影响 啮齿动物模型中的轴、VMS和睡眠障碍。这些科学努力将得到来自 我们的核心：睡眠资源核心(Klerman)将通过研究睡眠来扩大我们的科学影响 在人类和啮齿动物身上的结果。职业提升核心(力士乐/Rich-Edwards)将促进早期- 通过支持学者、试点项目、旅行交流，职业和新的性别差异研究人员 奖学金，以及强有力的教育计划。领导行政核心(约菲/曼森)将 提供科学和行政监督，并参与SCORE联盟。在现有的基础上， 卓有成效的合作，我们杰出的跨学科调查团队-女性健康、睡眠领域的领导者 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的强大资源 以及BWH的女性健康和睡眠协同项目。这一成绩将产生显著的 通过提高我们对应激在生产中的作用和机制的理解来影响公共健康 与老年妇女的心血管疾病和痴呆症易感性相关的生殖老龄化健康结局。

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.