Kapoor Amita, Matthews Stephen G
Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, M5S 1A8. Canada.
J Physiol. 2005 Aug 1;566(Pt 3):967-77. doi: 10.1113/jphysiol.2005.090191. Epub 2005 Jun 2.
Prenatal stress can have profound long-term influences on physiological function throughout the course of life. We hypothesized that focused periods of moderate prenatal stress at discrete time points in late gestation have differential effects on hypothalamo-pituitary-adrenal (HPA) axis function in adult guinea pig offspring, and that changes in HPA axis function will be associated with modification of anxiety-related behaviour. Pregnant guinea pigs were exposed to a strobe light for 2 h on gestational days (GD) 50, 51, 52 (PS50) or 60, 61, 62 (PS60) (gestation length approximately 70 days). A control group was left undisturbed throughout pregnancy. Behaviour was assessed in male offspring on postnatal day (PND)25 and PND70 by measurement of ambulatory activity and thigmotaxis (wall-seeking behaviour) in a novel open field environment. Subsequent to behavioural testing, male offspring were cannulated (PND75) to evaluate basal and activated HPA axis function. Body weight was significantly decreased in adult PS50 and PS60 offspring and this effect was apparent soon after weaning. The brain-to-body-weight ratio was significantly increased in adult PS50 males. Basal plasma cortisol levels were elevated in PS50 male offspring throughout the 24 h sampling period compared with controls. In response to an ACTH challenge and to exposure to an acute stressor, PS60 male offspring exhibited elevated plasma cortisol responses. Plasma testosterone concentrations were strikingly decreased in PS50 offspring. Thigmotaxis in the novel environment was increased in PS50 male offspring at PND25 and PND70, suggesting increased anxiety in these animals. In conclusion, prenatal stress during critical windows of neuroendocrine development programs growth, HPA axis function, and stress-related behaviour in adult male guinea pig offspring. Further, the nature of the effect is dependant on the timing of the maternal stress during pregnancy.
产前应激可对整个生命过程中的生理功能产生深远的长期影响。我们假设,在妊娠晚期的离散时间点进行的适度产前应激集中期,会对成年豚鼠后代的下丘脑-垂体-肾上腺(HPA)轴功能产生不同影响,并且HPA轴功能的变化将与焦虑相关行为的改变有关。怀孕的豚鼠在妊娠第50、51、52天(PS50)或第60、61、62天(PS60)(妊娠期约70天)暴露于频闪灯2小时。对照组在整个怀孕期间不受到干扰。通过在新的开放场环境中测量活动量和趋触性(靠墙行为),在出生后第25天(PND25)和第70天(PND70)对雄性后代的行为进行评估。行为测试后,对雄性后代进行插管(PND75)以评估基础和激活的HPA轴功能。成年PS50和PS60后代的体重显著降低,这种影响在断奶后不久就很明显。成年PS50雄性的脑体重比显著增加。与对照组相比,PS50雄性后代在整个24小时采样期内的基础血浆皮质醇水平升高。在促肾上腺皮质激素(ACTH)刺激和暴露于急性应激源时,PS60雄性后代表现出血浆皮质醇反应升高。PS50后代的血浆睾酮浓度显著降低。PS50雄性后代在PND25和PND70时在新环境中的趋触性增加,表明这些动物的焦虑增加。总之,在神经内分泌发育的关键窗口期的产前应激会影响成年雄性豚鼠后代的生长、HPA轴功能和应激相关行为。此外,影响的性质取决于孕期母体应激的时间。