{"title":"早期生活压力会损害恐惧记忆的获得和检索:性别效应、皮质酮调节,以及在青春期针对糖皮质激素受体的部分预防。","authors":"Jeniffer Sanguino-Gómez, Harm J. Krugers","doi":"10.1016/j.ynstr.2024.100636","DOIUrl":null,"url":null,"abstract":"<div><p>The early postnatal period is a sensitive time window that is characterized by several neurodevelopmental processes that define neuronal architecture and function later in life. Here, we examined in young adult mice, using an auditory fear conditioning paradigm, whether stress during the early postnatal period 1) impacts fear acquisition and memory consolidation in male and female mice; 2) alters the fear responsiveness to corticosterone and 3) whether effects of early-life stress (ELS) can be prevented by treating mice with a glucocorticoid (GR) antagonist at adolescence. Male and female mice were exposed to a limited nesting and bedding model of ELS from postnatal day (PND) 2–9 and injected i.p with RU38486 (RU486) at adolescent age (PND 28–30). At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. In conclusion, this study highlights the long-lasting consequences of early-life stress on fear memory processing and further illustrates 1) the potential of a glucocorticoid antagonist intervention during adolescence to mitigate these effects and 2) the partial modulation of the auditory retrieval upon post training administration of CORT, with all these effects being sex-dependent.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000328/pdfft?md5=f92e1654948ececd6ab47546667dad95&pid=1-s2.0-S2352289524000328-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age\",\"authors\":\"Jeniffer Sanguino-Gómez, Harm J. 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At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. 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引用次数: 0
摘要
产后早期是一个敏感的时间窗口,其特点是有多个神经发育过程,这些过程决定了以后的神经元结构和功能。在这里,我们利用听觉恐惧条件反射范例研究了成年小鼠在出生后早期的应激是否会:1)影响雄性和雌性小鼠的恐惧获得和记忆巩固;2)改变对皮质酮的恐惧反应性;3)是否可以通过在青春期用糖皮质激素(GR)拮抗剂治疗小鼠来预防早期生活应激(ELS)的影响。雄性和雌性小鼠从出生后第2-9天开始暴露于有限的筑巢和铺垫的ELS模型中,并在青春期(第28-30天)肌注RU38486(RU486)。在小鼠两个月大时,对其进行恐惧条件反射(FC)范式训练(训练后给予或不给予皮质酮-CORT),并对恐惧获得过程中的冻结行为以及上下文和听觉记忆检索进行评分。我们观察到,ELS会特别损害雄性小鼠的恐惧获得能力,并降低雄性和雌性小鼠的情境记忆和听觉记忆检索能力。训练后急性服用 CORT 会增加雌性小鼠在听觉记忆检索过程中的冻结水平,但却会降低尤其是对照组雄性小鼠在音调呈现过程中的冻结水平。用 RU486 治疗可防止雄性小鼠在习得过程中的 ELS 效应,以及雌性小鼠在听觉记忆检索过程中的 ELS 效应。总之,这项研究强调了早期生活压力对恐惧记忆处理的长期影响,并进一步说明了:1)在青春期使用糖皮质激素拮抗剂干预有可能减轻这些影响;2)在训练后服用 CORT 可部分调节听觉检索,所有这些影响都与性别有关。
Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age
The early postnatal period is a sensitive time window that is characterized by several neurodevelopmental processes that define neuronal architecture and function later in life. Here, we examined in young adult mice, using an auditory fear conditioning paradigm, whether stress during the early postnatal period 1) impacts fear acquisition and memory consolidation in male and female mice; 2) alters the fear responsiveness to corticosterone and 3) whether effects of early-life stress (ELS) can be prevented by treating mice with a glucocorticoid (GR) antagonist at adolescence. Male and female mice were exposed to a limited nesting and bedding model of ELS from postnatal day (PND) 2–9 and injected i.p with RU38486 (RU486) at adolescent age (PND 28–30). At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. In conclusion, this study highlights the long-lasting consequences of early-life stress on fear memory processing and further illustrates 1) the potential of a glucocorticoid antagonist intervention during adolescence to mitigate these effects and 2) the partial modulation of the auditory retrieval upon post training administration of CORT, with all these effects being sex-dependent.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.