Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Faculty of Social and Behavioural Sciences, Leiden University, Leiden, The Netherlands.
Genes Brain Behav. 2020 Sep;19(7):e12655. doi: 10.1111/gbb.12655. Epub 2020 Jun 15.
The differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7-repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4 mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2-14. Puberty onset was examined from P24 to P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4 mice exhibited the lowest and CN reared Drd4 mice the highest levels of licking/grooming. These results indicate that both genetic and early-environmental factors play an important role in shaping maternal care of the offspring for better and for worse.
易感性差异假说提出，那些更容易受到不良养育条件负面影响的个体，也可能从丰富的环境中获益更多。人类实验的证据表明，多巴胺受体 D4（DRD4）7 重复作为表现出这些好坏特征的主要因素，其效能较低。然而，人类研究缺乏动物实验提供的遗传和环境控制，这使得因果关系的评估变得复杂。为了在动物模型中研究易感性差异，我们在产后第 2-14 天（P）期间将 Drd4 小鼠和对照同窝仔鼠暴露于有限的巢/床（LN）、标准巢（SN）或群居巢（CN）饲养环境中。青春期的开始是从 P24 到 P36 进行检查，成年雌性动物则对其自身幼仔的母性照顾进行评估。在雄性和雌性中，LN 饲养的小鼠的青春期开始延迟，这部分是通过断奶时体重减轻来介导的，而与 Drd4 基因型无关。在成年期，LN 饲养的雌性表现出较差的母性照顾特征，而在 CN 环境中饲养的母鼠对其自身幼仔的不可预测性较低。只有雌性后代对其幼仔的舔舐/梳理水平才表现出易感性差异；LN 饲养的 Drd4 小鼠表现出最低的舔舐/梳理水平，而 CN 饲养的 Drd4 小鼠则表现出最高的舔舐/梳理水平。这些结果表明，遗传和早期环境因素都在塑造对后代的母性照顾方面发挥了重要作用，既有好的影响，也有坏的影响。
