Laboratory of Behavioral Neuroendocrinology, University of Tsukuba Tsukuba, Japan.
Department of Pharmacology, School of Medicine, Aichi Medical University Nagakute, Japan.
Front Neurosci. 2014 Sep 2;8:274. doi: 10.3389/fnins.2014.00274. eCollection 2014.
Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER) β plays a pivotal role in the regulation of stress responses and anxiety-related and social behaviors. Behavioral studies using ERβ knockout (βERKO) mice reported increased social investigation and decreased social anxiety in βERKO females, and elevated aggression levels in βERKO males compared to wild-type (WT) mice. In the present study, using βERKO and WT mice, we examined whether ERβ contributes to MS effects on anxiety and social behaviors. βERKO and WT mice were separated from their dam daily (4 h) from postnatal day 1-14 and control groups were left undisturbed. First, MS and ERβ gene deletion individually increased anxiety-related behaviors in the open field test, but only in female mice. Anxiety levels were not further modified in βERKO female mice subjected to MS stress. Second, βERKO female mice showed higher levels of social investigation compared with WT in the social investigation test and long-term social preference test. However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes. Third, peri-pubertal and adult βERKO male mice were more aggressive than WT mice as indicated by heightened aggression duration. On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice. Altogether, these results suggest that βERKO mice are sensitive to the adverse effects of MS stress on subsequent female and male social behaviors, which could then have overrode the ERβ effects on female social anxiety and male aggression.
母体分离（MS）是一种模拟早期生活应激对情绪和社会行为发展影响的动物模型。最近的研究表明，MS 应激增加了雌性小鼠的社交焦虑水平，并减少了雄性小鼠青春期前的攻击行为。雌激素受体（ER）β在应激反应以及焦虑相关和社会行为的调节中起着关键作用。使用 ERβ 敲除（βERKO）小鼠的行为研究报告称，βERKO 雌性小鼠的社交探索增加，社交焦虑减少，而βERKO 雄性小鼠的攻击水平升高。在本研究中，使用βERKO 和 WT 小鼠，我们研究了 ERβ 是否有助于 MS 对焦虑和社会行为的影响。βERKO 和 WT 小鼠从出生后第 1 天到第 14 天每天与母鼠分离（4 小时），对照组不受干扰。首先，MS 和 ERβ 基因缺失单独增加了开放式场测试中的焦虑相关行为，但仅在雌性小鼠中。在经历 MS 应激的βERKO 雌性小鼠中，焦虑水平没有进一步改变。其次，βERKO 雌性小鼠在社交探索测试和长期社交偏好测试中比 WT 表现出更高水平的社交探索。然而，MS 大大减少了 WT 和βERKO 雌性小鼠在社交探索测试中的社交探索持续时间，并增加了伸展接近的次数，表明两种基因型的社交焦虑水平升高。第三，青春期前和成年期的βERKO 雄性小鼠比 WT 小鼠更具攻击性，表现为攻击持续时间更长。另一方面，MS 显著降低了两种基因型的攻击持续时间，但仅在青春期前的雄性小鼠中。总之，这些结果表明，βERKO 小鼠对 MS 应激对随后的雌性和雄性社会行为的不良影响敏感，这可能掩盖了 ERβ 对雌性社交焦虑和雄性攻击的影响。
Zotero 插件
