Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland.
PLoS One. 2011;6(7):e21842. doi: 10.1371/journal.pone.0021842. Epub 2011 Jul 25.
Exposure to adverse environments during early development is a known risk factor for several psychiatric conditions including antisocial behavior and personality disorders. Here, we induced social anxiety and altered social recognition memory in adult mice using unpredictable maternal separation and maternal stress during early postnatal life. We show that these social defects are not only pronounced in the animals directly subjected to stress, but are also transmitted to their offspring across two generations. The defects are associated with impaired serotonergic signaling, in particular, reduced 5HT1A receptor expression in the dorsal raphe nucleus, and increased serotonin level in a dorsal raphe projection area. These findings underscore the susceptibility of social behaviors and serotonergic pathways to early stress, and the persistence of their perturbation across generations.
早期发育过程中暴露于不良环境是多种精神疾病的已知风险因素,包括反社会行为和人格障碍。在这里,我们通过不可预测的母婴分离和产后早期的母体应激诱导成年小鼠产生社交焦虑和改变社交识别记忆。我们表明,这些社交缺陷不仅在直接受到应激的动物中明显,而且还通过两代间传递到它们的后代中。这些缺陷与 5-羟色胺能信号传导受损有关,特别是背侧中缝核中的 5HT1A 受体表达减少,以及背侧中缝核投射区中的 5-羟色胺水平增加。这些发现强调了社交行为和 5-羟色胺能途径对早期应激的易感性,以及它们在代际间的持续存在。