Effects of estrogen on working memory during stress

雌激素对压力期间工作记忆的影响

• 批准号: 8996102
• 负责人: MARA MATHER
• 金额: $ 20.63万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8996102
• 关键词: Accounting; Affect; Affective; Aftercare; Aging; Animal Experimentation; Animals; Attenuated; Behavioral; Bilateral; Brain; Cerebrovascular Circulation; Cognition; Cognitive; Data; Elderly; Estradiol; Estrogens; Exhibits; Feedback; Health; Hippocampus (Brain); Hormones; Human; Hydrocortisone; Impairment; In Vitro; Intervention; Investigation; Laboratories; Lead; Learning; Left; Measures; Medical; Memory; Menopause; Menstrual cycle; Patients; Pattern; Performance; Phase; Physiological; Placebos; Play; Postmenopause; Prefrontal Cortex; Psychophysiology; Regulation; Research; Rest; Salivary; Sampling; Sex Characteristics; Short-Term Memory; Stress; Structure; System; Testing; Time; Tissues; Woman; Work; age related; aged; biological adaptation to stress; experience; heart rate variability; human female; in vivo; male; memory process; neuroimaging; protective effect; relating to nervous system; response; sex; stressor; young adult; young man; young woman

DESCRIPTION (provided by applicant): Stress often has detrimental effects on memory and cognition, effects that are especially challenging for older adults to sustain on top of existing age-related declines. In this project, we investigate whether estradiol (E2) protects against such effects. In humans E2 reduces the magnitude of the stress response and aids cognition. Further, in vitro and in vivo animal research shows that E2 protects the brain from the negative effects of stress hormones. Together, this pattern of results suggests the E2 may protect aging women's neural and cognitive integrity during times of stress. The current application tests this hypothesis by examining the effects of short-term E2 treatment on various systems affected by stress as well as testing a mechanism of action for E2 protection. First, we will examine the ability of a short-term E2 intervention to reduce physiological effects of stress, stress-induced impairments in working memory performance, and associated changes in brain activation. Work in our laboratory reveals that post-menopausal women with high salivary E2 levels as a result of taking E2 supplements release less of the stress hormone, cortisol, in response to a stressor than women with low salivary E2 levels. We also found that working memory performance in the high-E2 women was unhindered by stress, whereas low-E2 women performed significantly worse under stress than under control conditions. As a result of the E2-related reduction in stress hormone release we expect to find that E2 will be associated with 1) dampening the stress-induced changes in hippocampal cerebral blood flow and bilateral connectivity at rest during stress and control conditions, 2) smaller stress-induced decreases in heart-rate variability, and 3) hippocampal and prefrontal cortex activity while playing a working memory game. Second, we will test a potential mechanism of action for estradiol protection against stress. We hypothesize E2 limits vulnerability of the hippocampus to the effects of stress, allowing the hippocampus to effectively shut down the stress response, which curtails the levels of cortisol available and the amount of time cortisol is available to act on neural tissue. To test this we will compare estradiol and placebo groups on hippocampal cerebral blood flow and bilateral functional connectivity at rest, under stress and control conditions. These measures will be correlated with all estradiol levels, cortisol response, HRV, and working- memory-related brain activity and performance. The proposed research aims to uncover whether E2 can in fact reduce the negative effect of stress on memory in post-menopausal human females, as well as the brain mechanisms involved in this protection against stress. This research will further inform the medical field on the effects of E2 on stress and memory, which could lead to better guidance and advice for patients seeking information on E2 treatment during or after menopause.

描述（由申请人提供）：压力通常对记忆和认知的不利影响，对老年人在现有与年龄相关的下降之下维持尤其具有挑战性的影响。在这个项目中，我们研究雌二醇（E2）是否保护这种影响。在人类中，e2降低了压力反应的幅度并有助于认知。此外，体外和体内动物研究表明，E2可保护大脑免受应激激素的负面影响。总之，这种结果表明，在压力时期，E2可以保护妇女的神经和认知完整性。当前的申请通过检查短期E2处理对受压力影响的各种系统的影响以及测试E2保护的作用机理，从而检验了这一假设。首先，我们将研究短期E2干预措施减少压力的生理影响，压力引起的工作记忆力障碍以及大脑激活的相关变化的能力。在我们的实验室中的工作表明，与唾液E2水平低的妇女相比，唾液E2水平较高的唾液E2水平高的女性妇女释放了压力激素，皮质醇。我们还发现，高E2女性的工作记忆表现受到压力不受阻碍，而在压力下，低E2妇女的表现明显比对照条件下的较差。 As a result of the E2-related reduction in stress hormone release we expect to find that E2 will be associated with 1) dampening the stress-induced changes in hippocampal cerebral blood flow and bilateral connectivity at rest during stress and control conditions, 2) smaller stress-induced decreases in heart-rate variability, and 3) hippocampal and prefrontal cortex activity while playing a working memory game.其次，我们将测试雌二醇防止压力的潜在作用机理。我们假设E2限制了海马的脆弱性对压力的影响，从而使海马有效地关闭了应力反应，从而减少了可用的皮质醇水平，并且可以使用皮质醇的时间来对神经组织作用。测试 这将在压力和控制条件下，在静止状态下的海马脑血流和双边功能连通性上比较雌二醇和安慰剂组。这些措施将 与所有雌二醇水平，皮质醇反应，HRV以及与工作记忆相关的大脑活动和性能相关。拟议的研究旨在发现E2是否可以实际上可以减少绝经后人类女性的压力对记忆的负面影响，以及对这种防御压力的保护所涉及的大脑机制。这项研究将进一步向医学领域提供有关E2对压力和记忆力的影响的信息，这可能会为在更年期或之后寻求有关E2治疗信息的患者提供更好的指导和建议。