Department of Evolutionary and Functional Biology, University of Parma, Parma, Italy.
Stress. 2012 Jul;15(4):457-70. doi: 10.3109/10253890.2011.639414. Epub 2011 Dec 21.
Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans.
早期生活逆境会产生长期的生理和行为效应,并增强应激敏感性。本研究探讨了母体分离(MS)对成年期心脏应激反应性和结构的影响。雄性 Wistar 大鼠在出生后第 2 至 15 天期间,每天与母鼠分离 3 小时。当成年后暴露于 5 天间歇性束缚应激(IRS)时,MS 和对照组大鼠的心脏交感神经-迷走神经平衡的急性变化相似,通过心率变异性分析进行量化。此外,MS 对心脏起搏器的固有活动(通过东莨菪碱和阿替洛尔的自主阻断来揭示)没有影响,也不影响心率的昼夜节律性,无论是在 IRS 之前还是之后。然而,MS 与 IRS 后的对照组大鼠的心脏副交感神经驱动不同,后者的驱动增强,而前者不变,无论是在昼夜节律的亮期还是暗期。对成年心脏结构的评估表明,在关键发育阶段经历的应激仅引起适度的变化,涉及心肌细胞肥大、血管结构密度增加和心肌纤维化。这些功能-结构效应的轻微性质疑了 MS 作为人类早期应激诱导性心脏疾病模型的有效性。