Henningsen Kim, Dyrvig Mads, Bouzinova Elena V, Christiansen Sofie, Christensen Trine, Andreasen Jesper T, Palme Rupert, Lichota Jacek, Wiborg Ove
Centre for Psychiatric Research, Aarhus University Hospital, Aarhus, Denmark.
Behav Pharmacol. 2012 Dec;23(8):735-43. doi: 10.1097/FBP.0b013e32835a5184.
In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant tendency towards higher total cytosine methylation in rats from low maternal care dams. Assessment of methylation in the resilient versus anhedonic-like rat phenotypes, revealed only minor differences. Thus, maternal care status seems to be a strong predictor or trait marker for the behavioural phenotype.
在本研究中,我们报告了这样一个发现:当大鼠暴露于慢性轻度应激范式时,早期生活中母性关怀的质量会增加成年期对应激暴露的易感性。我们的结果表明,与低母性关怀相比,高母性关怀使大鼠具有不同的应激应对能力。因此,由低母性关怀的母鼠抚养的大鼠更容易形成应激易感表型,发展出类似快感缺失的状态。此外,低母性关怀的后代体重增加和运动能力较低,应激没有叠加效应。亚慢性暴露于慢性轻度应激会导致粪便皮质酮代谢产物增加,这仅在低母性关怀母鼠的后代中显著。对未受挑战的成年、具有母性特征的大鼠的糖皮质激素受体外显子17启动子甲基化进行检测,结果显示,低母性关怀母鼠的后代大鼠总胞嘧啶甲基化水平有升高趋势,但不显著。对具有恢复力的大鼠与类似快感缺失表型的大鼠的甲基化评估,仅发现微小差异。因此,母性关怀状态似乎是行为表型的一个强有力的预测指标或特征标记。