NeuroToxicology ( IF 3.4 ) Pub Date : 2018-04-06 , DOI: 10.1016/j.neuro.2018.04.005 Eleonora Gatta , Jérôme Mairesse , Lucie Deruyter , Jordan Marrocco , Gilles Van Camp , Hammou Bouwalerh , Jean-Marc Lo Guidice , Sara Morley-Fletcher , Ferdinando Nicoletti , Stefania Maccari
Exposure of the mother to adverse events during pregnancy is known to induce pathological programming of the HPA axis in the progeny, thereby increasing the vulnerability to neurobehavioral disorders. Maternal care plays a crucial role in the programming of the offspring, and oxytocin plays a key role in mother/pup interaction. Therefore, we investigated whether positive modulation of maternal behavior by activation of the oxytocinergic system could reverse the long-term alterations induced by perinatal stress (PRS; gestational restraint stress 3 times/day during the last ten days of gestation) on HPA axis activity, risk-taking behavior in the elevated-plus maze, hippocampal mGlu5 receptor and gene expression in Sprague-Dawley rats. Stressed and control unstressed dams were treated during the first postpartum week with an oxytocin receptor agonist, carbetocin (1 mg/kg, i.p.). Remarkably, reduction of maternal behavior was predictive of behavioral disturbances in PRS rats as well as of the impairment of the oxytocin and its receptor gene expression. Postpartum carbetocin corrected the reduction of maternal behavior induced by gestational stress as well as the impaired oxytocinergic system in the PRS progeny, which was associated with reduced risk-taking behavior. Moreover, postpartum carbetocin had an anti-stress effect on HPA axis activity in the adult PRS progeny and increased hippocampal mGlu5 receptor expression in aging. In conclusion, the activation of the oxytocinergic system in the early life plays a protective role against the programming effect by adverse experiences and could be considered as a novel and powerful potential therapeutic target for stress-related disorders.
中文翻译:
妊娠压力导致的孕产妇行为减少预示着由于压力/抗压力平衡的改变,冒险行为和基因表达的寿命会发生变化
已知母亲在怀孕期间暴露于不良事件会在子代中诱发HPA轴的病理程序设计,从而增加了对神经行为障碍的易感性。产妇保健在后代的编程中起着至关重要的作用,催产素在母亲/幼仔的相互作用中起着关键的作用。因此,我们研究了通过催产素系统的激活对母亲行为的正向调节是否可以逆转围产期应激(PRS;在妊娠的最后十天中,妊娠束缚应激每天3次/天)对HPA轴活动引起的长期变化, Sprague-Dawley大鼠在高架迷宫,海马mGlu5受体和基因表达中的冒险行为。在产后的第一阶段对有压力和无压力的水坝进行了处理催产素受体激动剂卡贝托星(1 mg / kg,腹膜内)。值得注意的是,产妇行为的减少预示着PRS大鼠的行为紊乱以及催产素及其受体基因表达的损伤。产后卡比妥星纠正了妊娠压力和PRS后代中催产素能系统受损引起的产妇行为的减少,这与冒险行为的减少有关。而且,产后Carbetocin对成年PRS后代的HPA轴活性具有抗应激作用,并在衰老过程中增加海马mGlu5受体的表达。总之,在早期生命中,催产素系统的激活起着防止编程作用的不良作用,可以被认为是与压力有关的疾病的一种新颖而强大的潜在治疗靶标。