ESTROGEN & AGING BRAIN

雌激素

• 批准号: 8357234
• 负责人: JOHN H MORRISON
• 金额: $ 7.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357234
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Animals; Brain; California; Cognition; Data; Estrogen Replacement Therapy; Estrogens; Event; Female; Funding; Goals; Grant; Hormone replacement therapy; Hormones; Hypothalamic structure; Link; Medial; Memory impairment; Menopause; Modeling; Modification; Molecular; National Center for Research Resources; Neurobiology; Physiological; Postmenopause; Primates; Principal Investigator; Progesterone; Regimen; Research; Research Infrastructure; Resources; Rodent Model; Schedule; Signal Transduction; Source; Spectrum Analysis; Synapses; System; Temporal Lobe; United States National Institutes of Health; Woman; Women' s Health; aged; aging brain; base; clinically relevant; cognitive enhancement; cognitive function; cost; human data; neural circuit; neurobehavioral; neurogenesis; neuropsychological; nonhuman primate; programs; reproductive; reproductive function; senescence

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary goal of this Program Project is to investigate interactions between the aging brain and female reproductive senescence. Animal studies have demonstrated clearly that changes in circulating estrogen levels affect cellular and molecular attributes of certain neural circuits and related cognitive functions. However, the link between such observations and the human data on peri- and post-menopausal memory impairment, beneficial neurobehavioral effects of estrogen replacement therapy (ERT) or combined hormone replacement therapy (HRT) and protection against Alzheimer's disease are far from clear. Recent studies from the Women's Health Initiative on potential negative effects of a commonly used combined hormone replacement (HR) regimen have brought these issues to the forefront, and reinforced the need for additional scientific data on which to base therapies that are more physiological and beneficial to women. The Program Project mechanism is ideally suited for a full spectrum analysis of the key issues; from signaling mechanisms of estrogen in the brain to an in-depth structural and functional assessment of the effects of estrogen on the circuits regulating reproductive function (hypothalamus), to the effects of estrogen and aging on cognition and related cortical circuits. Projects 1, 2, and 3 will converge on the rodent model for detailed mechanistic and ultrastructural analyses of estrogen-induced plasticity, interactions with progesterone, and alterations in estrogen-induced plasticity due to aging. Core A and Projects 2, 3, 4, and 5 will converge on the nonhuman primate model (NHP) to study similar systems in NHPs treated with one of several clinically relevant HR regimens involving different schedules of estrogen and progesterone replacement. The aged NHPs will have extensive neuropsychological assessment aimed at determining age, estrogen, and progesterone effects on medial temporal lobe and prefrontal functions. We will investigate the neurobiological effects of multiple HR regimens in young and aged NHPs to reveal key synaptic and cellular reflections of estrogen-induced plasticity as well as effects on neurogenesis, and potential modifications induced by progesterone. In the aged animals, we will illuminate the underlying neurobiological events responsible for cognitive enhancement.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该计划项目的主要目标是研究衰老的大脑与女性生殖衰老之间的相互作用。动物研究清楚地表明，循环雌激素水平的变化会影响某些神经回路和相关认知功能的细胞和分子属性。 然而，这些观察结果与围绝经期和绝经后记忆障碍、雌激素替代疗法（ERT）或联合激素替代疗法（HRT）的有益神经行为效应以及预防阿尔茨海默病的人类数据之间的联系还远不清楚。妇女健康倡议最近对常用的联合激素替代 (HR) 方案的潜在负面影响进行的研究使这些问题成为人们关注的焦点，并强调需要更多的科学数据来建立更生理和更有益的治疗方法。女性。 计划项目机制非常适合对关键问题进行全方位分析；从大脑中雌激素的信号传导机制到雌激素对调节生殖功能（下丘脑）回路的深入结构和功能评估，再到雌激素和衰老对认知和相关皮质回路的影响。项目 1、2 和 3 将集中在啮齿动物模型上，对雌激素诱导的可塑性、与黄体酮的相互作用以及雌激素诱导的可塑性因衰老而发生的变化进行详细的机制和超微结构分析。核心 A 和项目 2、3、4 和 5 将集中在非人类灵长类动物模型 (NHP) 上，研究接受几种临床相关 HR 方案之一（涉及不同雌激素和孕激素替代方案）治疗的 NHP 中的类似系统。老年 NHP 将进行广泛的神经心理学评估，旨在确定年龄、雌激素和孕激素对内侧颞叶和前额叶功能的影响。我们将研究多种 HR 方案对年轻和老年 NHP 的神经生物学影响，以揭示雌激素诱导的可塑性的关键突触和细胞反射，以及对神经发生的影响，以及黄体酮诱导的潜在修饰。在老年动物中，我们将阐明负责认知增强的潜在神经生物学事件。