Andersen Susan L, Teicher Martin H
Developmental Psychopharmacology Laboratory, Department of Psychiatry, Harvard Medical School, Belmont, MA, USA.
Neuropsychopharmacology. 2004 Nov;29(11):1988-93. doi: 10.1038/sj.npp.1300528.
Early maternal separation has been shown in animal models to produce enduring morphological changes in the hippocampus and other brain structures, which may not become evident until adulthood. Postnatally, the trajectory of overproduction and pruning of axons, dendrites, synapses and receptors shapes the brain between puberty and adulthood. The objective of the study was to ascertain whether this normal trajectory was affected by repeated maternal separation. Rat pups were separated from their mother for 4 h a day between postnatal days 2 and 20 (ISO group), and compared to rat pups that remained with their mother in the animal facilities (AFR group) and were exposed to minimal handling. Immunoreactivity to synaptophysin was quantified in the hippocampus CA1 and CA3, amygdala, and prefrontal cortex using optical densitometry (OD) at 25, 40, 60, 80, and 100 days in male and female rats. Synaptophysin OD increased dramatically in CA1 and CA3 between 25 and 60 days in the AFR group and fell by the same degree between 60 and 100 days, showing the expected sequence of overproduction and pruning. No difference between groups in synaptophysin OD was observed at 25 and 40 days. However, at day 60 synaptophysin was 34-36% lower in CA1 and CA3 of the ISO group, and remained 24-26% lower at 100 days. Early isolation produced no enduring reduction in synaptophysin OD in the amygdala or prefrontal cortex. Overall, these results suggest that early maternal separation produced a regionally specific delayed effect on the structure of the hippocampus by attenuating rates of synaptic development.
在动物模型中已表明，早期母婴分离会在海马体和其他脑结构中产生持久的形态变化，这些变化可能直到成年才会显现出来。出生后，轴突、树突、突触和受体的过度生成和修剪轨迹在青春期到成年期塑造了大脑。本研究的目的是确定这种正常轨迹是否会受到反复母婴分离的影响。将出生后第2天至第20天的幼鼠每天与母亲分离4小时（ISO组），并与留在动物饲养设施中与母亲在一起且极少受到处理的幼鼠（AFR组）进行比较。在雄性和雌性大鼠的25、40、60、80和100天时，使用光密度测定法（OD）对海马体CA1和CA3、杏仁核以及前额叶皮质中的突触素免疫反应性进行定量。在AFR组中，CA1和CA3区域的突触素OD在25至60天之间急剧增加，并在60至100天之间下降了相同程度，显示出预期的过度生成和修剪顺序。在25天和40天时，各组之间的突触素OD没有差异。然而，在第60天时，ISO组CA1和CA3区域的突触素降低了34 - 36%，在第100天时仍低24 - 26%。早期隔离在杏仁核或前额叶皮质中并未使突触素OD产生持久降低。总体而言，这些结果表明，早期母婴分离通过减弱突触发育速率，对海马体结构产生了区域特异性的延迟效应。
