Hormones and Learning and Memory

激素与学习和记忆

• 批准号: RGPIN-2018-04301
• 负责人: Galea, Liisa
• 金额: $ 5.76万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712908
• 关键词: Hormones; Learning; Memory

As anyone who has gone through adolescence, pregnancy, or aging can attest: hormones can exert powerful effects on brain and behaviour. My NSERC-related research has focussed on how hormones and biological sex can affect the brain to influence learning and memory. Why study sex differences in memory? Men and women differ in their susceptibility to develop memory problems, and show different brain responses to memory. For example, men are more likely to have memory problems with schizophrenia whereas women are more likely to have memory problems with depression or more severe memory loss with Alzheimer's disease. Hence, to gain a better understanding of how memories are formed in both sexes, it is important to acknowledge and study differences that might arise between both sexes in response to memory. Furthermore, estrogens, particularly estradiol, can exert profound effects on memory. There is a lot of controversy surrounding the use of estrogens to promote cognition in women, likely due to conflicting reports in the literature. We have found that estradiol, the most powerful of the estrogens, affects learning and memory differentially depending on the memory task and the amount estradiol given. High levels of estradiol impair both working (memory that changes from trial to trial, i.e. where you park your car every day) and reference memory (memory that stay stable over time, i.e where the parking lot is). However, low levels of estradiol facilitate working memory. These findings suggest that estradiol has different effects on learning dependent on the dose given with positive effects on working memory but detrimental effects on reference memory. The hippocampus, an important brain area for memory, produces new brain cells throughout the lifespan in rodents and humans and these new cells play a crucial role in different forms of memory. We found that males and females differ in the hippocampus's response to memory, as well as we see differences in the production of new cells in response when females have different levels of estrogens. These findings suggest that there are different pathways that are involved in learning and memory between the sexes and/or with different levels of estradiol. In this proposal, we plan to study how both factors (sex and estradiol) affect where and how learning and memory occurs in the brain. We will examine 1) activation of the hippocampus and other brain areas after memory, 2) how new brains cells respond to memory, and 3) whether the mechanisms in the brain cells driving memory are different in males and females, or females with different levels of estradiol. Understanding how biological sex and hormones can influence memory, may lead to a better understanding of how learning and memory is organized in the brain in both males and females, and ultimately of why some people are more susceptible to memory problems than others.

正如任何经历过青春期、怀孕或衰老的人都可以证明的那样：激素可以对大脑和行为产生强大的影响。我的NSERC相关研究集中在荷尔蒙和生物性别如何影响大脑，从而影响学习和记忆。为什么要研究记忆中的性别差异？男性和女性患记忆问题的敏感度不同，大脑对记忆的反应也不同。例如，男性更有可能患有精神分裂症的记忆问题，而女性更有可能患有抑郁症或阿尔茨海默病的更严重的记忆力丧失。因此，为了更好地了解两性记忆是如何形成的，承认和研究两性对记忆的反应可能出现的差异是很重要的。此外，雌激素，特别是雌二醇，可以对记忆产生深远的影响。关于使用雌激素来促进女性的认知，有很多争议，很可能是因为文献中相互矛盾的报道。我们已经发现，雌二醇是最强大的雌激素，根据记忆任务和给予雌二醇量的不同，对学习和记忆的影响是不同的。高水平的雌二醇会损害工作记忆(随着试验的不同而变化的记忆，即你每天把车停在哪里)和参考记忆(随着时间的推移保持稳定的记忆，即停车场在哪里)。然而，低水平的雌二醇会促进工作记忆。这些发现表明，雌二醇对学习有不同的影响，依赖于给药的剂量，对工作记忆有积极影响，但对参考记忆有不利影响。海马体是大脑中重要的记忆区域，在啮齿动物和人类的一生中都会产生新的脑细胞，这些新细胞在不同形式的记忆中发挥着至关重要的作用。我们发现，男性和女性的海马体对记忆的反应不同，我们也看到，当女性的雌激素水平不同时，新细胞的产生也不同。这些发现表明，不同性别和/或不同水平的雌二醇参与学习和记忆的途径不同。在这项提案中，我们计划研究这两个因素(性别和雌二醇)如何影响学习和记忆在大脑中发生的位置和方式。我们将研究1)记忆后海马体和其他脑区的激活，2)新的脑细胞如何对记忆做出反应，3)脑细胞驱动记忆的机制在男性和女性中是否有所不同，或者雌二醇水平不同的女性是否有所不同。了解生理性别和荷尔蒙如何影响记忆，可能有助于更好地理解学习和记忆是如何在男性和女性的大脑中组织的，并最终理解为什么有些人比其他人更容易受到记忆问题的影响。