Psychophysiological investigation of 17ß-estradiol effects on memory functions under stress in humans

17α-雌二醇对人类压力下记忆功能影响的心理生理学研究

• 批准号: RGPIN-2019-06901
• 负责人: Duchesne, Annie
• 金额: $ 2.04万
• 依托单位: University of Northern British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764001
• 关键词: Psychophysiological; investigation; 17; estradiol; effects

How we attend, learn, encode and retrieve elements of the world varies within and between individuals. Evidence from animals and humans supports the regulatory role of 17ß-estradiol (E2) on multiple memory processes. Specifically, the effects of E2 have been documented for working memory and episodic memory, and for the recruitment of different memory systems. However, the existing evidence does not support the role of E2 on women's memory processes, with studies failing to observe an effect of circulating E2 on memory. Overlooked in humans is evidence, including some from my own research, that supports the interactive effect of stress and ovarian hormones in predicting behaviour. Furthermore, stress exposure has been shown to regulate the same memory domains as E2; substantial animal evidence confirms the interactive effects of E2 and stress on memory processes. The degree of acute stress (mild vs. moderate) as well as the chronicity of stress have all been found to moderate effects of E2 on memory processes. Finally, evidence from both animals and humans suggests that the interactive effects of E2 and stress on memory processes might be mediated by increased activity in physiological stress systems, particularly the sympathetic nervous system. My long term objective is to develop a bio-behavioural model of E2 effects in humans that accounts for environmental and individual variations (also called a context by person model). The end result of this program is to explain when, how and in whom changes in E2 levels impacts behaviour. First, to investigate how environmental factors shape the effect of E2 on women's memory functions, my short term objectives are to empirically validate and elucidate the behavioural and physiological effects of E2 under stress. To do so, the combined effects of acute stress and natural variation in E2 levels on specific memory processes (working memory, episodic memory and memory system recruitment) will be investigated. Similarly, how varying levels of chronic stress exposure regulate the effect of E2 on memory processes will be assessed. Finally, possible mediating effects of the physiological stress systems will be assessed. These experiments will serve as the foundation for my research program which I plan to expand in three main directions: 1) mechanistically through pharmacological manipulation 2) neurophysiologically with the use of technologies such as electroencephalography and 3) behaviorally by investigating other cognitive processes such as fear extinction and cognitive flexibility. Reconciling systematic inconsistencies within and between human and animal literature, this research program will lay the groundwork for the development of a context by person model of E2 effects on behavior. Ultimately, this work will have broader implications for understanding inter- and intra-individual differences in cognitive functions and their manifestation in educational, personal or occupational contexts.

我们如何参与，学习，编码和检索世界的元素在个体内部和个体之间各不相同。来自动物和人类的证据支持17 β-雌二醇（E2）对多种记忆过程的调节作用。具体而言，E2的影响已被记录为工作记忆和情景记忆，以及不同记忆系统的招募。然而，现有的证据并不支持E2对女性记忆过程的作用，研究未能观察到循环E2对记忆的影响。 在人类中被忽视的是证据，包括我自己的一些研究，支持压力和卵巢激素在预测行为方面的相互作用。此外，压力暴露已被证明可以调节与E2相同的记忆域;大量的动物证据证实了E2和压力对记忆过程的交互作用。急性应激的程度（轻度与中度）以及应激的长期性都被发现可以减轻E2对记忆过程的影响。最后，来自动物和人类的证据表明，E2和压力对记忆过程的相互作用可能是由生理压力系统，特别是交感神经系统的活动增加介导的。 我的长期目标是开发一个E2对人类影响的生物行为模型，该模型考虑了环境和个体差异（也称为个人模型）。该计划的最终结果是解释E2水平的变化何时，如何以及在谁影响行为。首先，调查环境因素如何塑造E2对女性记忆功能的影响，我的短期目标是实证验证和阐明E2在压力下的行为和生理效应。为此，将研究急性应激和E2水平自然变化对特定记忆过程（工作记忆、情景记忆和记忆系统募集）的综合影响。同样，如何不同程度的慢性应激暴露调节E2对记忆过程的影响将进行评估。最后，将评估生理应激系统可能的介导作用。这些实验将作为我的研究计划的基础，我计划在三个主要方向上扩展：1）通过药理学操作的机制，2）神经生理学使用技术，如脑电图和3）通过调查其他认知过程，如恐惧消退和认知灵活性的行为。 在人类和动物文献中以及人类和动物文献之间的系统性不一致，这项研究计划将为E2对行为影响的个人模型的背景发展奠定基础。最终，这项工作将有更广泛的影响，了解认知功能的个体间和个体内的差异及其在教育，个人或职业环境中的表现。