Neurodegeneration Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
Behav Brain Res. 2012 May 16;231(1):29-39. doi: 10.1016/j.bbr.2012.02.040. Epub 2012 Mar 3.
Prenatal stress and associated in utero exposure to elevated levels of stress hormones can adversely affect the development of the central nervous system, thereby increasing the risk of mental illnesses in later life. Here, we examined the impact of prenatal exposure to chronic mild stress (CMS) on locomotion, anxiety-related behaviour, cognition and hippocampal serotonergic neurotransmission in juvenile and adult B6D2F2 mice, and whether antidepressant treatment in adulthood could reverse the observed behavioural disturbances. Pregnant B6D2F1 female mice were either subjected to CMS or left undisturbed until parturition. Three-week and 7-week-old male and female offspring were assessed in the open-field, novel object recognition and contextual fear conditioning tests. Hippocampal levels of serotonin and its major metabolite were then quantified using high-performance liquid chromatography. Some prenatally-stressed adult females were treated with amitriptyline (20mg/kg/day in drinking water) for 10 days, from the day prior to onset of behavioural testing. In a separate experiment, amniotic fluid was collected from stressed and non-stressed dams on gestational (G) days 13 and 18 to quantify levels of corticosterone. We found that prenatal CMS specifically impaired learning and memory performance in adult females. Amitriptyline elevated hippocampal serotonin levels and attenuated these cognitive deficits. Corticosterone levels in the amniotic fluid were increased by CMS on G13 but by G18, the levels in non-stressed dams reached those of stressed dams. These results suggest that female mice are particularly vulnerable to the adverse developmental effects of prenatal stress which can be improved by appropriate treatment strategies including antidepressants.
产前应激和与之相关的宫内暴露于高水平应激激素会对中枢神经系统的发育产生不利影响，从而增加日后患精神疾病的风险。在这里，我们研究了产前慢性轻度应激（CMS）暴露对 B6D2F2 幼鼠和成年鼠运动、焦虑相关行为、认知和海马 5-羟色胺能神经传递的影响，以及成年期抗抑郁治疗是否可以逆转观察到的行为障碍。怀孕的 B6D2F1 雌性小鼠要么接受 CMS 处理，要么在分娩前不受干扰。3 周和 7 周龄的雄性和雌性幼鼠在旷场、新物体识别和情境恐惧条件反射测试中进行评估。然后使用高效液相色谱法定量海马中 5-羟色胺及其主要代谢物的水平。一些产前应激的成年雌性用阿米替林（20mg/kg/天在饮用水中）治疗 10 天，从行为测试开始前一天开始。在另一个实验中，从应激和非应激母鼠的羊水在妊娠（G）天 13 和 18 日收集皮质酮的水平。我们发现，产前 CMS 特异性损害成年雌性的学习和记忆能力。阿米替林升高了海马 5-羟色胺水平并减轻了这些认知缺陷。CMS 在 G13 日增加了羊水中的皮质酮水平，但在 G18 日，非应激母鼠的水平达到了应激母鼠的水平。这些结果表明，雌性小鼠特别容易受到产前应激的不利发育影响，适当的治疗策略，包括抗抑郁药，可以改善这些影响。
