Shin Sangyep, Lee Sukwon
Developmental Disorders and Rare Disease Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.
Front Mol Neurosci. 2023 May 24;16:1147951. doi: 10.3389/fnmol.2023.1147951. eCollection 2023.
Neonatal maternal separation is a widely used method to construct an early-life stress model in rodents. In this method, pups are separated from their mothers for several hours every day during the first 2 weeks of life, which results in adverse early-life events. It is a known fact that maternal separation can exert a significant impact on the behavior and psychological health, such as anxiety and depression, in adolescent offspring. However, environmental conditions during maternal separation can differ such as the presence of other animals or by placing pups in a different dam. To investigate the differential effects of various conditions of maternal separation on the behavior of adolescent mice, we created the following groups: (1) iMS group: pups were moved to an isolated room with no other adult mice in a nearby cage, (2) eDam group: the pups randomly exchanged their dams, (3) OF group: pups were shifted to another cage with the bedding material containing maternal odor (olfactory stimulation), and (4) MS group: pups were shifted to another vivarium. From postnatal day (PND) 2-20 (i.e., 19 consecutive days), pups were separated from the dam daily for 4 h and exposed to various environments (MS, iMS, eDam, and OF) or were left undisturbed [control (CON) group]. A series of behavioral assessments were conducted to evaluate locomotion, anxiety, recognition, learning, and memory in adolescent offspring. The results showed that neonatal maternal separation led to impaired recognition memory, motor coordination, and motor skill learning across all groups. However, the iMS group exhibited anxiety-like behavior in the elevated plus maze test and enhanced the extinction of fear memory in the auditory fear conditioning test. The OF and eDam groups displayed partially recovered short-term working memory in the Y-maze test but exhibited opposite exploratory behaviors. The OF group spent more time in the center, while the eDam group spent less time. These findings demonstrated that exposure to different environmental conditions during maternal separation causes behavioral alterations in adolescent offspring, providing a potential explanation for the variation in behavioral phenotypes observed in the early-life stress models.
新生鼠母婴分离是在啮齿动物中构建早期生活应激模型的一种广泛使用的方法。在这种方法中，幼崽在出生后的前2周每天与母亲分离数小时，这会导致不良的早期生活事件。众所周知，母婴分离会对青春期后代的行为和心理健康产生重大影响，如焦虑和抑郁。然而，母婴分离期间的环境条件可能不同，例如是否有其他动物在场，或者将幼崽放在不同的母鼠身边。为了研究母婴分离的各种条件对青春期小鼠行为的不同影响，我们创建了以下几组：(1) iMS组：将幼崽转移到一个隔离的房间，附近笼子里没有其他成年小鼠；(2) eDam组：幼崽随机更换母鼠；(3) OF组：将幼崽转移到另一个装有含有母鼠气味的垫料的笼子里（嗅觉刺激）；(4) MS组：将幼崽转移到另一个饲养室。从出生后第2天到第20天（即连续19天），幼崽每天与母鼠分离4小时，并暴露于各种环境（MS、iMS、eDam和OF）中，或者不受干扰[对照组（CON）]。进行了一系列行为评估，以评估青春期后代的运动、焦虑、识别、学习和记忆。结果表明，新生鼠母婴分离导致所有组的识别记忆、运动协调和运动技能学习受损。然而，iMS组在高架十字迷宫试验中表现出焦虑样行为，并在听觉恐惧条件反射试验中增强了恐惧记忆的消退。OF组和eDam组在Y迷宫试验中显示出部分恢复的短期工作记忆，但表现出相反的探索行为。OF组在中央花费更多时间，而eDam组花费较少时间。这些发现表明，母婴分离期间暴露于不同的环境条件会导致青春期后代的行为改变，为早期生活应激模型中观察到的行为表型差异提供了一个潜在的解释。
