Weiss Isabelle C, Franklin Tamara B, Vizi Sándor, Mansuy Isabelle M
Brain Research Institute, University of Zurich/Swiss Federal Institute of Technology Zurich, Switzerland.
Front Behav Neurosci. 2011 Feb 4;5:3. doi: 10.3389/fnbeh.2011.00003. eCollection 2011.
The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development induces poor and disorganized maternal care, and results in behavioral deficits that persist through adulthood. Here, we examined the long-term effect of unpredictable maternal separation combined with maternal stress on behavior and its transmissibility. We report that unpredictable maternal separation from birth to postnatal day 14 in C57Bl/6J mice has mild behavioral effects in the animals when adult, but that its combination with maternal stress exacerbates this effect. Further, the behavioral deficits are transmitted to the following generation through females, an effect that is independent of maternal care and is not affected by cross-fostering. The combined manipulation does not alter basic components of the hypothalamic-pituitary-adrenal axis but decreases the expression of the corticotropin releasing factor receptor 2 (CRFR2) in several nuclei of the amygdala and the hypothalamus in the brain of maternal-separated females. These results suggest a non-genomic mode of transmission of the impact of early stress in mice.
早期应激对人类行为和情绪的长期影响已有充分记录，并且可以在实验动物中进行模拟。在小鼠中，出生后早期发育期间的母婴分离会导致母性照顾不佳且紊乱，并导致行为缺陷持续到成年期。在此，我们研究了不可预测的母婴分离与母体应激相结合对行为及其可遗传性的长期影响。我们报告称，在C57Bl/6J小鼠中，从出生到出生后第14天进行不可预测的母婴分离，成年后对动物有轻微行为影响，但与母体应激相结合会加剧这种影响。此外，行为缺陷通过雌性传递给下一代，这种影响独立于母性照顾，且不受交叉寄养的影响。联合操作不会改变下丘脑-垂体-肾上腺轴的基本组成部分，但会降低母婴分离雌性小鼠大脑中杏仁核和下丘脑几个核团中促肾上腺皮质激素释放因子受体2（CRFR2）的表达。这些结果表明小鼠早期应激影响存在非基因组传递模式。
