What kind of neural circuit in the brain of prenatally stressed offspring may be responsible to the vulnerabill to chronic stress in adulthood

有人认为，早期不良生活事件，包括童年虐待，忽视，和父母的损失可能倾向于个人的发展情感障碍，以应对极端的压力暴露在成年期。最近，我们已经证明，产前盐水注射应激产生了增强肾上腺皮质对条件性恐惧应激的反应，并延长了强迫游泳应激的不动持续时间，表明产前应激的后代似乎在成年后的内分泌和行为上对急性应激具有抵抗性。目前还不清楚产前应激的大鼠是否能在成年后适应慢性应激。本实验研究了14天重复束缚应激对产前应激成年雄性大鼠脑内c-fos mRNA表达和皮质酮分泌的应激反应。在急性束缚应激条件下，与对照组相比，产前应激组大鼠室旁核、杏仁核、蓝斑、中缝核、扣带皮质、梨状皮质和隔垫等脑区c-fos mRNA表达显著增加。与急性束缚应激时c-fos mRNA的表达相比，重复束缚应激14 d后，除隔区外，其余脑区c-fos反应均显著降低。在隔，产前应激大鼠表现出显着增加c-fos的表达在重复约束应激反应，与对照组相比。此外，对照组大鼠显示出减少血浆皮质酮水平在120分钟后开始束缚应激从第7天的压力，而产前应激大鼠没有表现出这种习惯。这些结果表明，包括隔在内的神经回路可能与产前应激大鼠成年后对慢性应激的耐受性有关。

It has been suggested that early adverse life events including childhood abuse, neglect, and parental loss may predispose individuals for the development of affective disorders in response to extreme stress exposure in adulthood. Recently, we have demonstrated that the prenatal saline injection stress produced an enhanced adrenocortical response to conditioned fear stress and a prolonged immobility duration in forced swimming stress, indicating that the prenatally stressed offspring seemed to be susceptive to an acute stress in adulthood endocrinologically and behaviorally. It is still unclear whether prenatally stressed rats can habituate to chronic stress in adulthood. We have investigated the stress response of c-fos mRNA expression in brain and of corticosterone secretion in prenatally stressed adult male rats during 14 days repeated restraint stress. To an acute restraint stress, prenatally stressed rats showed significantly increased response of c-fos mRNA expression, to the same extent, compared to control rats, in brain regions including para-ventricular nucleus, amygdala, locus ceruleus, raphe nucleus, cingulate cortex, piriform cortex, and seputum. Repeated restraint stress for 14 days induced significant reduction of c-fos response, compared to the expession of c-fos mRNA during acute restraint stress, in all investigated brain regions except septum of prenatally stressed rats. In septum, prenatally stressed rats showed significant increase in c-fos expression in response to repeated restraint stress, compared to control rats. In addition, control rats showed reduction of plasma corticosterone level at 120min after the beginning of restraint stress from the 7th day of stress, whereas prenatally stressed rats did not show such habituation. These findings indicate that the neural circuit including septum may be responsible to the vulnerabillty of prenatally stressed rats to chronic stress in adulthood.