Effects of hormones and menopausal transitions on hippocampal structure and function

激素和更年期过渡对海马结构和功能的影响

• 批准号: 9903187
• 负责人: ALISON CLEMENTS BURGGREN
• 金额: $ 15.6万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903187
• 关键词: Address; Affect; Age; Aging; Agreement; Alzheimer' s Disease; Animal Model; Animals; Area; Brain; Cognition; Cognitive; Collaborations; Complex; Data; Data Collection; Data Set; Databases; Diagnosis; Disease; Elderly; Enrollment; Estradiol; Estrogen Receptors; Estrogens; Event; Exposure to; Follicle Stimulating Hormone; Functional Magnetic Resonance Imaging; Funding; Hippocampus (Brain); Hormonal; Hormone replacement therapy; Hormones; Human; Imaging Device; Impaired cognition; Incidence; Injury; Intervention; Investigation; Light; Luteinizing Hormone; Magnetic Resonance Imaging; Measures; Mediating; Memory; Memory Loss; Memory impairment; Menopausal Status; Menopause; Modeling; Moods; Nerve Degeneration; Neurobehavioral Manifestations; Neurons; Participant; Performance; Perimenopause; Play; Pyramidal Cells; Questionnaires; Rattus; Receptor Activation; Recording of previous events; Research Support; Resolution; Risk; Role; Sampling; Secure; Serum; Severities; Sex Differences; Sleep; Source; Staging; Structure; Surveys; Symptoms; Synaptic plasticity; Techniques; Testing; Testosterone; Thinness; Time; Woman; Work; age related; base; cognitive change; cognitive function; cohort; connectome; experience; follow up assessment; high resolution imaging; hippocampal pyramidal neuron; hippocampal subregions; hormone therapy; in vivo; insight; magnetic field; memory encoding; men; middle age; nervous system disorder; prevent; prospective; protective factors; recruit; structured data; tool; web app

ABSTRACT Age-related changes in hormone levels occur in both men and women but are more pronounced in women approaching menopause, typically between the ages of 45 to 52 years old 1. Despite prior data addressing brain-aging differences in women and men, how hormone changes in midlife affect brain structure and cognition in women remains unclear. Women appear to be more vulnerable to cognitive decline during this peri-menopausal period 2, and there is general agreement that women experience memory deficits during this timeframe 3–6. Estrogen-depletion is widely regarded as a likely cause of cognitive impairment in peri-menopausal women 7 but the mechanistic understanding of how declining estrogen rates affect cognitive decline and brain changes is relatively poorly understood. In animal models, estrogen receptors are found throughout the brain, but predominate in limbic-related areas that play a crucial role in cognitive function 8. Specifically, these animal studies show hippocampal subfields Cornu Ammonis 1, 2, and 3 as densely populated regions of estrogen-receptors; activation of these estrogen-receptors has been shown to mediate estrogen's beneficial effect on synaptic plasticity as well as play a role in preventing neurodegeneration in hippocampal neurons 9,10. We propose here investigating the impact of declining estrogen levels on hippocampal structure and function in peri-menopausal women as part of our collaboration with the Human Connectome Project- Aging (HCP-A). This project makes use of the rigorously structured data collection pipeline HCP-A is using to objectively stage menopause data points. Although the data detailed here are being collected as part of the HCP-A project, with 103 subjects currently available and an additional 107 anticipated to be recruited over the coming 2 years, no support for subsequent investigations is included as part of the HCP-A; investigations proposing to answer scientific questions using the dataset must be funded with separate research support. Specifically, we will analyze high-field magnetic resonance imaging (MRI) data of the hippocampus in order to assess memory structures and function in fine detail and determine whether lower estrogen levels predict poorer memory performance in peri-menopausal women. We will also investigate whether hormone replacement therapy has a beneficial effect at mediating the effect of changes in estrogen levels in midlife women. We expect results from this project to shed light on the complex relationship between changes in hormone levels and subsequent effects on hippocampal structure and memory function in midlife.

抽象的 男性和女性都会出现与年龄相关的激素水平变化，但女性更为明显 接近更年期，通常年龄在 45 岁至 52 岁之间 1. 尽管之前的数据表明 女性和男性的大脑老化差异、中年时期的激素变化如何影响大脑结构以及 女性的认知能力仍不清楚，在此期间女性似乎更容易出现认知能力下降。 围绝经期 2，人们普遍认为女性在此期间会出现记忆缺陷 时间范围 3-6。雌激素消耗被广泛认为是围绝经期女性认知障碍的可能原因 7，但对雌激素水平下降如何影响认知的机制理解 在动物模型中，人们对雌激素受体的衰退和大脑变化知之甚少。 遍布整个大脑，但主要集中在边缘系统相关区域，这些区域在认知功能中发挥着至关重要的作用 8. 具体来说，这些动物研究表明海马亚区 Cornu Ammonis 1、2 和 3 的密度相同 雌激素受体密集区域；这些雌激素受体的激活已被证明可以介导 雌激素对突触可塑性有益，并在预防神经退行性变中发挥作用 海马神经元 9,10。 我们在此建议研究雌激素水平下降对海马结构的影响 作为我们与人类连接组项目合作的一部分，它对围绝经期妇女发挥作用- 老化 (HCP-A) 该项目利用 HCP-A 所使用的严格结构化的数据收集管道。 尽管这里详细的数据是作为更年期数据点的一部分收集的。 HCP-A 项目，目前有 103 名受试者，预计将在未来招募另外 107 名受试者 未来 2 年内，HCP-A 调查中不会包含对后续调查的支持； 提议使用数据集回答科学问题必须由单独的研究资助 具体来说，我们将分析高场磁共振成像（MRI）数据。 海马体，以便详细评估记忆结构和功能，并确定是否 较低的雌激素水平预示着围绝经期女性的记忆力较差。 研究激素替代疗法是否对调节体内变化的影响具有有益作用 我们期望该项目的结果能够揭示这一复杂情况。 激素水平变化与随后对海马结构的影响之间的关系 中年时期的记忆功能。