Central Institute of Mental Health, Mannheim, Germany.
PLoS One. 2011 Apr 28;6(4):e19218. doi: 10.1371/journal.pone.0019218.
Depressive episodes are frequently preceded by stressful life events. Evidence from genetic association studies suggests a role for the glucocorticoid receptor (GR), an essential element in the regulation of stress responses, in the pathophysiology of the disorder. Since the stress response system is affected by pregnancy and postpartum-associated changes, it has also been implicated in the pathophysiology of postpartum depression. Using a 2 × 2 factorial design, we investigated whether a heterozygous deletion of GR would influence maternal care behavior in C57BL/6 and Balb/c mice, two inbred strains known to display qualitative differences in this behavior. Behavioral observation was carried out between postnatal days 1 and 7, followed by a pup retrieval test on postnatal days 7 or 8. While previously noted inter-strain differences were confirmed for different manifestations of caring behavior, self-maintenance and neglecting behaviors as well as the pup retrieval test, no strain-independent effect of the GR mutation was noted. However, an interaction between GR genotype and licking/grooming behavior was observed: it was down-regulated in heterozygous C57BL/6 mice to the level recorded for Balb/c mice. Home cage observation poses minimal disturbance of the dam and her litter as compared to more invasive assessments of dams' emotional behavior. This might be a reason for the absence of any overall effects of the GR mutation, particularly since GR heterozygous animals display a depressive-like phenotype under stressful conditions only. Still, the subtle effect we observed may point towards a role of GR in postpartum affective disorders.
抑郁发作常与生活应激事件相关。遗传关联研究的证据表明,糖皮质激素受体(GR)在该疾病的病理生理学中起重要作用,GR 是应激反应调节的一个基本要素。由于应激反应系统受到妊娠和产后相关变化的影响,它也与产后抑郁症的病理生理学有关。我们采用 2×2 析因设计,研究了 GR 杂合缺失是否会影响 C57BL/6 和 Balb/c 两种近交系小鼠的母性行为,这两种近交系在这种行为上表现出定性差异。行为观察在产后第 1 天至第 7 天之间进行,然后在产后第 7 天或第 8 天进行幼仔回收测试。虽然之前注意到了不同的照顾行为、自我维持和忽视行为以及幼仔回收测试方面的种间差异得到了证实,但 GR 突变没有表现出与种系无关的影响。然而,GR 基因型和舔舐/梳理行为之间存在相互作用:在杂合 C57BL/6 小鼠中,这种行为被下调到 Balb/c 小鼠的水平。与对母鼠情绪行为进行更具侵入性的评估相比,笼内观察对母鼠及其幼仔的干扰最小。这可能是 GR 突变没有产生任何整体影响的原因,特别是因为 GR 杂合动物只有在应激条件下才表现出类似抑郁的表型。尽管如此,我们观察到的微妙影响可能表明 GR 在产后情感障碍中的作用。