The impact of maternal neglect on genetic hyperactivity.
The impact of maternal neglect on genetic hyperactivity.
复制标题
DOI：
10.1016/j.bbr.2016.07.033
复制
发表时间：
2016-10-15
影响因子：
2.7
通讯作者：
Rhodes JS
中科院分区：
文献类型：
--
作者：
Majdak P;Grogan EL;Gogola JV;Sorokina A;Tse S;Rhodes JS
早期的环境条件越来越被认为是塑造行为和认知的关键。有证据表明，有压力的养育环境可能对成年后的行为产生持久的影响，但很少有研究探讨养育环境可能加剧遗传性多动障碍的可能性。发现环境对多动症传播的强烈影响可以为转化研究提供新的途径。最近，我们开发了一种选择性繁殖的高活性小鼠系来模拟ADHD，为解决环境传播问题提供了独特的资源。高活性品系显示跨代多动，但出生后环境（即母体提供的母体护理）对多动的影响尚未系统量化。本研究采用交叉寄养方法，同时解决1）在早期环境中是否为高活跃和对照幼仔提供了相似水平的护理，以及2）饲养环境的任何差异是否会影响多动行为。与对照组相比，高活性母鼠表现出母体能力的所有指标受损，这降低了存活率，并显著降低了后代在生命早期和断奶时的体重。虽然高活性母鼠提供的恶化的产后环境最终足以抑制对照组的活动，但高活性后代的多动性仍不受饲养条件的影响。这些数据不仅证实了遗传学影响多动跨代的力量，而且还提供了证据表明，早期饲养环境可能不会对多动表型的极端影响。
Early environmental conditions are increasingly appreciated as critical in shaping behavior and cognition. Evidence suggests that stressful rearing environments can have an enduring impact on behaviors in adulthood, but few studies have explored the possibility that rearing environment could exacerbate genetic hyperactivity disorders. Uncovering a strong environmental influence on the transmission of hyperactivity could provide novel avenues for translational research. Recently we developed a selectively bred High-Active line of mice to model ADHD, providing a unique resource to address the question of environmental transmission. The High-Active line demonstrates transgenerational hyperactivity, but the influence of the postnatal environment (i.e. maternal care provided by dams) on hyperactivity had not been systemically quantified. This study employed a cross-fostering method to simultaneously address 1) whether High-Active and Control pups are provided with similar levels of care in the early environment, and 2) whether any differences in rearing environment influence hyperactive behavior. High-Active dams demonstrated impairment in all measures of maternal competence relative to Controls, which reduced survival rates and significantly reduced the body mass of offspring in early life and at weaning. While the deteriorated postnatal environment provided by High-Active dams was ultimately sufficient to depress Control activity, the hyperactivity of High-Active offspring remained unaffected by fostering condition. These data not only confirm the power of genetics to influence hyperactivity across generations, but also provide evidence that early rearing environments may not have a significant impact on the extreme end of hyperactive phenotypes.